Unraveling MYC’s Role in Orchestrating Tumor Intrinsic and Tumor Microenvironment Interactions Driving Tumorigenesis and Drug Resistance

Round 1

Reviewer 1 Report

The paper delivers an insightful and detailed review of the transcription factor MYC, highlighting its central role in the regulation of various cellular processes, especially its implication in tumorigenesis across different cancer types. The comprehensive overview touches on the multifaceted dimensions of MYC, encompassing its influence on tumor intrinsic characteristics and the tumor microenvironment. The review is well-grounded in the current literature, making it an up-to-date resource for researchers and clinicians interested in MYC-driven oncogenesis. 

 

I recommend it for publication. However, the authors should consider expanding the discussion to include the interplay between RAS and MYC. For instance, RAS can suppress Myc-induced apoptosis, and reciprocally, Myc can abrogate Ras-induced senescence. Despite being a downstream target in the RAS pathway, the cooperation between MYC and RAS in tumorigenesis has been long been recognized. Engaging in these discussions would provide further insights into the complex role of MYC in tumor development.

Author Response

Thank you for your feedback. We greatly appreciate your insightful suggestion regarding the interplay between RAS and MYC in tumor development. We have expanded the our review to encompass the intricate interplay between RAS and MYC. This addition enhances the comprehensiveness of our work and provides readers with a deeper understanding of the complex role that MYC plays in tumorigenesis. Once again, we sincerely appreciate your valuable input, and we believe that your suggestion has contributed to the overall quality of our manuscript. Thank you for your time and consideration.

Reviewer 2 Report

The draft is well organized and informative. However, there are some key references missing and some editing are required before considering it further. 

1. I recommend to add an "Introduction" before "The physiological function of MYC", which will explain the necessity of the work in the field. Please also add the "Objectives of the current study".

2. Two key references are missing. Couple of works from Hong Wan's team, showed the role of junctional protein Dsg3 in cancer migration and invasion. They used Dsg3 full length (FL) and its C-terminally truncated proteins (lacking the transmembrane domain and cytoplasmic tail) denoted, respectively, all of which are tagged with a Myc epitope at C-terminus. The second article showed the variances in different tumor microenvironment models, which is directly relevant to this review.

https://doi.org/10.1080/19336918.2016.1195942 

https://doi.org/10.1016/j.yexcr.2018.06.037

At the end please include e a section on "Discussion" which will include conclusion and future direction.

Author Response

Reviewer #2, Comments and Suggestions for Authors:

The draft is well organized and informative. However, there are some key references missing and some editing are required before considering it further.

 

1. I recommend to add an "Introduction" before "The physiological function of MYC", which will explain the necessity of the work in the field. Please also add the "Objectives of the current study".

Thank you for your review and valuable suggestions. We have incorporated an "Objectives" section into the manuscript to clarify the purpose and scope of our study. Regarding the "Introduction," we have chosen to keep it concise, as we have introduced the key points in the abstract to avoid redundancy and ensure the focus on the main content. We believe these changes enhance the clarity and flow of our paper.

2. Two key references are missing. Couple of works from Hong Wan's team, showed the role of junctional protein Dsg3 in cancer migration and invasion. They used Dsg3 full length (FL) and its C-terminally truncated proteins (lacking the transmembrane domain and cytoplasmic tail) denoted, respectively, all of which are tagged with a Myc epitope at C-terminus. The second article showed the variances in different tumor microenvironment models, which is directly relevant to this review.

 

https://doi.org/10.1080/19336918.2016.1195942

 

https://doi.org/10.1016/j.yexcr.2018.06.037

 

At the end please include e a section on "Discussion" which will include conclusion and future direction.

• We appreciate your feedback and your attention to detail. We acknowledge the works from Hong Wan's team that you mentioned, which explore the role of junctional protein Dsg3 in cancer migration and invasion. However, our review specifically focuses on Myc biology and its implications in tumor development. While these references utilized a Myc epitope tag for protein detection, we agree that they may not directly contribute to the understanding of Myc's biological functions as discussed in our review. We are committed to ensuring the accuracy and relevance of the content in our review. Thank you once again for your thoughtful review.

 

• "Discussion" section which include conclusion and future direction now added to the reviow.

Round 2

Reviewer 2 Report

Recommend to accept in current form.