Modulation of Spheroid Forming Capacity and TRAIL Sensitivity by KLF4 and Nanog in Gastric Cancer Cells
, Qui Anh Le 1,2,†, Hang Thi Thuy Bui 1,2, Ji-Hong Park 1,2 and Dongchul Kang 1,2,*
Round 1
Reviewer 1 Report
This study investigated that the association of pluripotency factors (OCT4, Nanog, SOX2 and KLF4) with clinicopathological parameters of gastric cancer patients. In addition, authors describe their expression upon stem cell-enriching spheroid culture of gastric cancer cells and regulation of response to cisplatin and TRAIL treatments by Nanog and KLF4. There are some issues that need to be addressed.
1. For Figure 2.C, why doesn’t use the same β-actin as reference.
2. Why did the authors choose the cell line SNU-638 over the more obvious SNU-668?
3. The author should indicate whether the cells used in Figure 3 are parental cells or spheroid-culture cells.
4. In response to the different killing effects of cisplatin on the two cell lines in Figure 3 A, cisplatin caused a decrease in KLF4 on the third day, according to the subsequent knockdown overexpression test, did KLF4 continue to decline or recover when it continued to decline on the 5th and 7th days? Similarly with TRAIL treatment, the change in KLF4 expression level with the duration of treatment administration should be detected.
Author Response
A pdf file titled 'cimb-2040320_Response to Reviewer 1' was attached.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The manuscript “modulation of spheroid forming capacity and TRAIL sensitivity by KLF4 and Nanog in gastric cancer cells” described the pluripotency factors with clinicopathological parameters of gastric cancer patients. The manuscript is clear, well written, and well interpretated. In addition, this study advances the knowledge and should be published at Curr. Issues Mol. Biol with minor review.
1) Authors should avoid the use of “we” or “our” (e.g., “we report association.” should be replaced to “this study reported the association…” ).
2) Use the past tense along the manuscript.
3) Authors should add a conclusion section in the end of the manuscript. The text from line 509 should be added in the conclusion.
4) Data Availability Statement. Please, delete redundant information. I suggest to include “The data will be available on request”
Author Response
A pdf file titled 'cimb-2040320_Response to Reviewer 2' was attached.
Author Response File: Author Response.pdf
Reviewer 3 Report
In this MS, authors suggested that KLF4 overexpression increased spheroid formation, susceptibility to cisplatin and TRAIL treatment and DR4/DR5 expression in gastric cancer SNU- 638 cells (KLF4/Nanog-low). Despite interesting data, it has some concerns as follows:
1. Why do you choose SNU-638 (KLF low) rather than SNU484 or SNU668 compared to SNU-601 in your study?
2. Show the viability of SNU484 or SNU668 transfected with KLF overexpression vector
3. Show endogenous level of OCT4 and SOX2 in Figure 2C
4. Why were SNU601 cells not sensitive to TRAIL treatment compared to SNU638 cells different from cisplatin treatment, provided that KLF4 increased TRAIL sensitivity?
5. Check English expression and grammar. e.g, cell viabilities were measured by MTT assay.
Author Response
A pdf file titled 'cimb-2040320_Response to Reviewer 3' was attached.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The explanations and revise are acceptable afterward.
Author Response
Reviewer's comment: 'The explanations and revise are acceptable afterward.'
Response: We deeply appreciate your encouraging comment on the revised manuscript. Thanks to your thoughtful suggestions, we could improve quality of our manuscript significantly. Thank you for taking time to go over the manuscript carefully and to advise us with productive suggestions.
