Reviewer’s report
Title: 
SMC1A facilitates gastric cancer cell proliferation, migration and invasion
via promoting SNAIL activated EMT
Version: 
2 
Date: 
02 Apr 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Maybe - with major revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: Gastric cancer can be quite devastating and therefore
there is a need to better understand its progression, including the process of
EMT. Authors have characterized the role of SMC1A in gastric cancer and
provided some mechanistic studies. There is need to provide more clarity and
show more data to make the mechanism more convincing. Here are my
suggestions -
There are numerous typos and errors. The very first word of Abstract should be
'Structural' instead of 'structural'. A few statements later. 'Recent studies
demonstrated that SMC1A participate…' should be edited to 'Recent studies
demonstrated that SMC1A participates…'. Later in the Abstract. The statement
'While knockdown of SMC1A in HCG27 inhibited cell proliferation, migration
and invasion of HGC27 cells.' Needs to be first edited so that it does not start
with 'while' - the first mention of HCG27 should be edited to HCG27 cells. 'our'
should be edited to 'Our' at the start of Conclusion of Abstract. The whole
statement in Conclusion of the Abstract needs to be rewritten. In the very first
sentence of the Background, 'Gastric cancer (GC) as one' should be edited to
'Gastric cancer (GC) is one' - later in that sentence, 'seriously damages human
health' does not make grammatical sense - please edit. 
These are just a few
examples of errors in language and grammar at the very beginning of article. The
errors are distracting and its difficult to focus on the article. I will not comment
on such errors now but I hope that the authors will get the manuscript carefully
edited to rectify all such errors throughout the manuscript.
At one point in the Background section, authors mention 'In gastric cancer, little
is known regarding the possible function of SMC1A.'. It needs to be specified
what all is known, with proper citations. 
Please list the p-value in Fig 1C - is the difference statistically significant?
Result from 4 cell lines is shown in Fig 1E but the methods section only
describes culture conditions for 2?
Why were AGS cells chosen for gain of function study - why not GES-1?
Were multiple siRNAs tested in HGC27 cells for their relative silencing of
SMC1A? If yes, please show results.
In the Results section, while discussing the in vivo results, authors mentioned -
'To further confirm the role of SMC1A on the tumorigenesis of GC cells in vivo,
xenografts in nude mice were performed. Tumor volume, growth rate and weight
were clearly increased in SMC1A overexpression group compared to the control
group' This write-up does not provide any information on which cell line was
used etc and the description is too brief. Please elaborate on findings and provide
all relevant information right here so that the readers do not have to refer to other
sections to get the information.
After writing the previous comment, I looked at the Methods section to find
relevant information. Apparently, the authors used AGS cells which begs the
question - why not HGC27 cells that have higher endogenous levels of SMC1A?
For the western blots in Figure 3A and 3B, please show densitometric analysis.
Authors write 'Besides, the similar results were seen by immunofluorescence
assay (Figure 3C and 3D)'. This needs to be corrected to convey correct
information. In its present form, this statement seems to convey the message that
whatever is shown in western blots in Figure 3B is shown by
immunofluorescence in Figures 3C-D. This is not completely correct because
western blots show E-cadherin, vimentin and N-cadherin while
immunofluorescence only shows E-cadherin and Vimentin. 
In Figures 3E-F western blots, authors show that restoring SNAIL can rescue si-
SMC1A effects. This needs to be shown by immunofluorescence as well.
For Figures 3E-F, please mention the name of cell lines right here in the Results.
Similarly, while describing the results from Fig 4, please mention the name of
cell line.
In Figure 3E, what is vector? Ideally, authors should have shown SNAIL
expression in a) siNC, b) si-SMC1A and c) si-SMC1A+SNAIL
In the tumor samples shown in Figure 2F, authors need to show the status of
SNAIL as well as EMT markers.
The mechanistic studies consist of silencing SMC1A and hen rescuing through
overexpression of SNAIL. Authors also need to show the converse - i.e.
overexpress SMC1A and silence SNAIL. This is critical.
REQUESTED REVISIONS: 
Please refer to my detailed feedback to authors
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Web of Science Reviewer Recognition
. Springer Nature can send verification
of this review directly to a Web of Science researcher profile (a subsidiary of
Clarivate Analytics). If you would like to take advantage of this service, please
click on the “Yes” option below. Your name, email address, title of the reviewed
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“Review Data”) will then be transmitted to Web of Science after the final
decision on the manuscript has been made. If you have already registered with
Web of Science for a 
Web of Science researcher profile (this service was
previously known as “Publons”), they will notify you of the receipt of this
review and update your profile as per your settings and their policy. If you are
not registered with Web of Science, you will receive an email from them asking
you to register in order for them to be able to recognize your review on your new
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metadata for the benefit of Web of Science and you as a reviewer, carefully
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may verify your record as a reviewer by updating your profile published on its
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candidate reviewers. Please find the details of processing in Web of Science’s
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policy/
No
Reviewer’s report
Title: 
SMC1A facilitates gastric cancer cell proliferation, migration and invasion
via promoting SNAIL activated EMT
Version: 
2 
Date: 
02 Apr 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Maybe - with major revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: Gastric cancer can be quite devastating and therefore
there is a need to better understand its progression, including the process of
EMT. Authors have characterized the role of SMC1A in gastric cancer and
provided some mechanistic studies. There is need to provide more clarity and
show more data to make the mechanism more convincing. Here are my
suggestions -
There are numerous typos and errors. The very first word of Abstract should be
'Structural' instead of 'structural'. A few statements later. 'Recent studies
demonstrated that SMC1A participate…' should be edited to 'Recent studies
demonstrated that SMC1A participates…'. Later in the Abstract. The statement
'While knockdown of SMC1A in HCG27 inhibited cell proliferation, migration
and invasion of HGC27 cells.' Needs to be first edited so that it does not start
with 'while' - the first mention of HCG27 should be edited to HCG27 cells. 'our'
should be edited to 'Our' at the start of Conclusion of Abstract. The whole
statement in Conclusion of the Abstract needs to be rewritten. In the very first
sentence of the Background, 'Gastric cancer (GC) as one' should be edited to
'Gastric cancer (GC) is one' - later in that sentence, 'seriously damages human
health' does not make grammatical sense - please edit. 
These are just a few
examples of errors in language and grammar at the very beginning of article. The
errors are distracting and its difficult to focus on the article. I will not comment
on such errors now but I hope that the authors will get the manuscript carefully
edited to rectify all such errors throughout the manuscript.
At one point in the Background section, authors mention 'In gastric cancer, little
is known regarding the possible function of SMC1A.'. It needs to be specified
what all is known, with proper citations. 
Please list the p-value in Fig 1C - is the difference statistically significant?
Result from 4 cell lines is shown in Fig 1E but the methods section only
describes culture conditions for 2?
Why were AGS cells chosen for gain of function study - why not GES-1?
Were multiple siRNAs tested in HGC27 cells for their relative silencing of
SMC1A? If yes, please show results.
In the Results section, while discussing the in vivo results, authors mentioned -
'To further confirm the role of SMC1A on the tumorigenesis of GC cells in vivo,
xenografts in nude mice were performed. Tumor volume, growth rate and weight
were clearly increased in SMC1A overexpression group compared to the control
group' This write-up does not provide any information on which cell line was
used etc and the description is too brief. Please elaborate on findings and provide
all relevant information right here so that the readers do not have to refer to other
sections to get the information.
After writing the previous comment, I looked at the Methods section to find
relevant information. Apparently, the authors used AGS cells which begs the
question - why not HGC27 cells that have higher endogenous levels of SMC1A?
For the western blots in Figure 3A and 3B, please show densitometric analysis.
Authors write 'Besides, the similar results were seen by immunofluorescence
assay (Figure 3C and 3D)'. This needs to be corrected to convey correct
information. In its present form, this statement seems to convey the message that
whatever is shown in western blots in Figure 3B is shown by
immunofluorescence in Figures 3C-D. This is not completely correct because
western blots show E-cadherin, vimentin and N-cadherin while
immunofluorescence only shows E-cadherin and Vimentin. 
In Figures 3E-F western blots, authors show that restoring SNAIL can rescue si-
SMC1A effects. This needs to be shown by immunofluorescence as well.
For Figures 3E-F, please mention the name of cell lines right here in the Results.
Similarly, while describing the results from Fig 4, please mention the name of
cell line.
In Figure 3E, what is vector? Ideally, authors should have shown SNAIL
expression in a) siNC, b) si-SMC1A and c) si-SMC1A+SNAIL
In the tumor samples shown in Figure 2F, authors need to show the status of
SNAIL as well as EMT markers.
The mechanistic studies consist of silencing SMC1A and hen rescuing through
overexpression of SNAIL. Authors also need to show the converse - i.e.
overexpress SMC1A and silence SNAIL. This is critical.
REQUESTED REVISIONS: 
Please refer to my detailed feedback to authors
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Web of Science Reviewer Recognition
. Springer Nature can send verification
of this review directly to a Web of Science researcher profile (a subsidiary of
Clarivate Analytics). If you would like to take advantage of this service, please
click on the “Yes” option below. Your name, email address, title of the reviewed
manuscript, name of the journal, and date of your review submission (the
“Review Data”) will then be transmitted to Web of Science after the final
decision on the manuscript has been made. If you have already registered with
Web of Science for a 
Web of Science researcher profile (this service was
previously known as “Publons”), they will notify you of the receipt of this
review and update your profile as per your settings and their policy. If you are
not registered with Web of Science, you will receive an email from them asking
you to register in order for them to be able to recognize your review on your new
profile page. Web of Science may use the Review Data to generate derivative
metadata for the benefit of Web of Science and you as a reviewer, carefully
considering the sensitivity of such information. For example, Web of Science
may verify your record as a reviewer by updating your profile published on its
webservice if you have registered for such service or help editors to identify
candidate reviewers. Please find the details of processing in Web of Science’s
privacy policy 
https://clarivate.com/privacy-center/notices-policies/privacy-
policy/
No
Please review this paper.
user
Reviewer’s report
Title: 
SMC1A facilitates gastric cancer cell proliferation, migration and invasion
via promoting SNAIL activated EMT
Version: 
2 
Date: 
02 Apr 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Maybe - with major revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: Gastric cancer can be quite devastating and therefore
there is a need to better understand its progression, including the process of
EMT. Authors have characterized the role of SMC1A in gastric cancer and
provided some mechanistic studies. There is need to provide more clarity and
show more data to make the mechanism more convincing. Here are my
suggestions -
There are numerous typos and errors. The very first word of Abstract should be
'Structural' instead of 'structural'. A few statements later. 'Recent studies
demonstrated that SMC1A participate…' should be edited to 'Recent studies
demonstrated that SMC1A participates…'. Later in the Abstract. The statement
'While knockdown of SMC1A in HCG27 inhibited cell proliferation, migration
and invasion of HGC27 cells.' Needs to be first edited so that it does not start
with 'while' - the first mention of HCG27 should be edited to HCG27 cells. 'our'
should be edited to 'Our' at the start of Conclusion of Abstract. The whole
statement in Conclusion of the Abstract needs to be rewritten. In the very first
sentence of the Background, 'Gastric cancer (GC) as one' should be edited to
'Gastric cancer (GC) is one' - later in that sentence, 'seriously damages human
health' does not make grammatical sense - please edit. 
These are just a few
examples of errors in language and grammar at the very beginning of article. The
errors are distracting and its difficult to focus on the article. I will not comment
on such errors now but I hope that the authors will get the manuscript carefully
edited to rectify all such errors throughout the manuscript.
At one point in the Background section, authors mention 'In gastric cancer, little
is known regarding the possible function of SMC1A.'. It needs to be specified
what all is known, with proper citations. 
Please list the p-value in Fig 1C - is the difference statistically significant?
Result from 4 cell lines is shown in Fig 1E but the methods section only
describes culture conditions for 2?
Why were AGS cells chosen for gain of function study - why not GES-1?
Were multiple siRNAs tested in HGC27 cells for their relative silencing of
SMC1A? If yes, please show results.
In the Results section, while discussing the in vivo results, authors mentioned -
'To further confirm the role of SMC1A on the tumorigenesis of GC cells in vivo,
xenografts in nude mice were performed. Tumor volume, growth rate and weight
were clearly increased in SMC1A overexpression group compared to the control
group' This write-up does not provide any information on which cell line was
used etc and the description is too brief. Please elaborate on findings and provide
all relevant information right here so that the readers do not have to refer to other
sections to get the information.
After writing the previous comment, I looked at the Methods section to find
relevant information. Apparently, the authors used AGS cells which begs the
question - why not HGC27 cells that have higher endogenous levels of SMC1A?
For the western blots in Figure 3A and 3B, please show densitometric analysis.
Authors write 'Besides, the similar results were seen by immunofluorescence
assay (Figure 3C and 3D)'. This needs to be corrected to convey correct
information. In its present form, this statement seems to convey the message that
whatever is shown in western blots in Figure 3B is shown by
immunofluorescence in Figures 3C-D. This is not completely correct because
western blots show E-cadherin, vimentin and N-cadherin while
immunofluorescence only shows E-cadherin and Vimentin. 
In Figures 3E-F western blots, authors show that restoring SNAIL can rescue si-
SMC1A effects. This needs to be shown by immunofluorescence as well.
For Figures 3E-F, please mention the name of cell lines right here in the Results.
Similarly, while describing the results from Fig 4, please mention the name of
cell line.
In Figure 3E, what is vector? Ideally, authors should have shown SNAIL
expression in a) siNC, b) si-SMC1A and c) si-SMC1A+SNAIL
In the tumor samples shown in Figure 2F, authors need to show the status of
SNAIL as well as EMT markers.
The mechanistic studies consist of silencing SMC1A and hen rescuing through
overexpression of SNAIL. Authors also need to show the converse - i.e.
overexpress SMC1A and silence SNAIL. This is critical.
REQUESTED REVISIONS: 
Please refer to my detailed feedback to authors
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Web of Science Reviewer Recognition
. Springer Nature can send verification
of this review directly to a Web of Science researcher profile (a subsidiary of
Clarivate Analytics). If you would like to take advantage of this service, please
click on the “Yes” option below. Your name, email address, title of the reviewed
manuscript, name of the journal, and date of your review submission (the
“Review Data”) will then be transmitted to Web of Science after the final
decision on the manuscript has been made. If you have already registered with
Web of Science for a 
Web of Science researcher profile (this service was
previously known as “Publons”), they will notify you of the receipt of this
review and update your profile as per your settings and their policy. If you are
not registered with Web of Science, you will receive an email from them asking
you to register in order for them to be able to recognize your review on your new
profile page. Web of Science may use the Review Data to generate derivative
metadata for the benefit of Web of Science and you as a reviewer, carefully
considering the sensitivity of such information. For example, Web of Science
may verify your record as a reviewer by updating your profile published on its
webservice if you have registered for such service or help editors to identify
candidate reviewers. Please find the details of processing in Web of Science’s
privacy policy 
https://clarivate.com/privacy-center/notices-policies/privacy-
policy/
No
assistant