Cancer Biology

VPS9D1-AS1 overexpression amplifies intratumoral TGF-β signaling and promotes tumor cell escape from CD8+ T cell killing in colorectal cancer

1. Lei Yang
2. Xichen Dong
3. Zheng Liu
4. Jinjing Tan
5. Xiaoxi Huang
6. Tao Wen
7. Hao Qu
8. Zhenjun Wang

• Curated by eLife

  eLife assessment

  This research focuses on the role of a long noncoding RNA VPS9D1-AS1(VPS) in colorectal cancer (CRC) immune evasion and provides evidence on how it is responsible for escape from cytotoxic T cells killing via amplifying intra-tumoral TGF-β signaling. The findings are of considerable translational significance since VPS9D1-AS1 was validated targetable in this work, and it is of broad interest to readers in cancer biology and immunotherapy.

Reviewed by eLife

Defining function of wild-type and three patient-specific TP53 mutations in a zebrafish model of embryonal rhabdomyosarcoma

1. Jiangfei Chen
2. Kunal Baxi
3. Amanda E Lipsitt
4. Nicole Rae Hensch
5. Long Wang
6. Prethish Sreenivas
7. Paulomi Modi
8. Xiang Ru Zhao
9. Antoine Baudin
10. Daniel G Robledo
11. Abhik Bandyopadhyay
12. Aaron Sugalski
13. Anil K Challa
14. Dias Kurmashev
15. Andrea R Gilbert
16. Gail E Tomlinson
17. Peter Houghton
18. Yidong Chen
19. Madeline N Hayes
20. Eleanor Y Chen
21. David S Libich
22. Myron S Ignatius

• Curated by eLife

  eLife Assessment:

  This manuscript sheds light on the biology of embryonal rhabdomyosarcoma, a common pediatric muscle tumor, by exploiting an established zebrafish model. Specifically, new knowledge is revealed of how the p53 tumor suppressor contributes to progression and extent of disease. This paper will be of interest not only to pediatric oncologists but also the broader cancer research community given the frequency of TP53 mutations as secondary lesions in human cancer.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Clonal transcriptomics identifies mechanisms of chemoresistance and empowers rational design of combination therapies

1. Sophia A Wild
2. Ian G Cannell
3. Ashley Nicholls
4. Katarzyna Kania
5. Dario Bressan
6. CRUK IMAXT Grand Challenge Team
7. Gregory J Hannon
8. Kirsty Sawicka

• Curated by eLife

  eLife Assessment:

  This manuscript describes a highly novel barcoding strategy for forward genetic lineage tracing of tumor cells in vitro and in the in vivo environment. The technique, coined WILDseq, can be used to track cells present in vitro which are enriched or depleted in the in vivo environment. Treatment further contributes to clonal expansion and retraction and emergence of populations with sensitivity to alternate agents. The studies are rigorously conducted and are highly impactful.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

Beta human papillomavirus 8E6 promotes alternative end joining

1. Changkun Hu
2. Taylor Bugbee
3. Rachel Palinski
4. Ibukun A Akinyemi
5. Michael T McIntosh
6. Thomas MacCarthy
7. Sumita Bhaduri-McIntosh
8. Nicholas Wallace

• Curated by eLife

  Evaluation Summary:

  This manuscript reports useful data on how human papillomavirus 8E6 protein regulates DSB repair pathways in human cells. The data support the claim that 8E6 promotes alternative end-joining through binding and destabilizing the p300 acetyltransferase, but the study remains relatively descriptive and incomplete as it is not yet clear which alternative end-joining pathway is involved lacking a test of a direct involvement of DNA polymerases theta (POLθ).

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

FOXP2 confers oncogenic effects in prostate cancer

1. Xiaoquan Zhu
2. Chao Chen
3. Dong Wei
4. Yong Xu
5. Siying Liang
6. Wenlong Jia
7. Jian Li
8. Yanchun Qu
9. Jianpo Zhai
10. Yaoguang Zhang
11. Pengjie Wu
12. Qiang Hao
13. Linlin Zhang
14. Wei Zhang
15. Xinyu Yang
16. Lin Pan
17. Ruomei Qi
18. Yao Li
19. Feiliang Wang
20. Rui Yi
21. Ze Yang
22. Jianye Wang
23. Yanyang Zhao

• Curated by eLife

  Evaluation Summary:

  The authors identify a new FOXP2-CPED1 gene fusion in prostate cancer that leads to the increased expression of FOXP2 and subsequent transformation of non-cancer cells. Increased FOXP2 was shown to promote prostate cancer in part through the increased expression and activation of the receptor tyrosine kinase MET, a known driver of prostate cancer. Notably, the authors created new genetically engineered mouse models of FOXP2 and FOXP2-CPED1 overexpression in prostate luminal epithelial cells which was sufficient to cause prostatic intraepithelial neoplasia in these mice with lesions that confirmed increased MET signaling. Oncogenes are typically interesting drug targets or interact with possible drug targets, and the manuscript could thus have a significant societal impact on better understanding drivers of the disease.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

SHARPIN S146 phosphorylation mediates ARP2/3 interaction, cancer cell invasion and metastasis

1. Umar Butt
2. Meraj H. Khan
3. Jeroen Pouwels
4. Jukka Westermarck

Reviewed by Review Commons

YAP / BRD4 ‐controlled ROR1 promotes tumor‐initiating cells and hyperproliferation in pancreatic cancer

1. Masaya Yamazaki
2. Shinjiro Hino
3. Shingo Usuki
4. Yoshihiro Miyazaki
5. Tatsuya Oda
6. Mitsuyoshi Nakao
7. Takaaki Ito
8. Kazuya Yamagata

Reviewed by Review Commons

Covalent disruptor of YAP-TEAD association suppresses defective Hippo signaling

1. Mengyang Fan
2. Wenchao Lu
3. Jianwei Che
4. Nicholas P Kwiatkowski
5. Yang Gao
6. Hyuk-Soo Seo
7. Scott B Ficarro
8. Prafulla C Gokhale
9. Yao Liu
10. Ezekiel A Geffken
11. Jimit Lakhani
12. Kijun Song
13. Miljan Kuljanin
14. Wenzhi Ji
15. Jie Jiang
16. Zhixiang He
17. Jason Tse
18. Andrew S Boghossian
19. Matthew G Rees
20. Melissa M Ronan
21. Jennifer A Roth
22. Joseph D Mancias
23. Jarrod A Marto
24. Sirano Dhe-Paganon
25. Tinghu Zhang
26. Nathanael S Gray

• Curated by eLife

  Evaluation Summary:

  Fan and colleagues disclose the development of covalent TEAD inhibitors and they report on the therapeutic potential of this class of agents in the treatment of TEAD-YAP-driven cancers (e.g., malignant pleural mesothelioma, MPM). Optimized derivatives of a previously reported covalent TEAD inhibitor are described and characterized, using diverse profiling approaches that range from biochemical and cell-based assays to X-ray co-crystallographic analysis and in vivo efficacy in a relevant mouse xenograft model. The manuscript represents an impressive and deep characterization of this small molecule class. The authors' claims and conclusions are very well supported and justified by the data, although differentiation from a very closely related compound termed K-975 is not entirely clear as currently presented.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair

1. Judit Jimenez-Sainz
2. Joshua Mathew
3. Gemma Moore
4. Sudipta Lahiri
5. Jennifer Garbarino
6. Joseph P Eder
7. Eli Rothenberg
8. Ryan B Jensen

• Curated by eLife

  Evaluation Summary:

  This study provides a thorough functional analysis of three mutations in the BRCA2 gene that do not seem to necessarily cause breast cancer. The authors use functional assays in cancer cells and with recombinant proteins to determine that two BRCA2 variants, S1221P and T1980I, are indeed pathogenic, while the T13461 variant is fully functional and benign. The strength of the study is the rigorous assessment of these mutations in a variety of established assays for BRCA2. The work is likely to have a broad impact in the breast cancer field.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM)

1. Ling Zhong
2. Peng Hao
3. Qian Zhang
4. Tao Jiang
5. Huan Li
6. Jialing Xiao
7. Chenglong Li
8. Lan Luo
9. Chunbao Xie
10. Jiang Hu
11. Liang Wang
12. Yuping Liu
13. Yi Shi
14. Wei Zhang
15. Bo Gong

• Curated by eLife

  Evaluation Summary:

  This paper is of potential interest to a broad audience across myeloma study and single cell technology, as it implies a major adjustment to our current understanding of pathogenesis and treatment of myeloma. Overall the data quality is good, although reasonable alternative explanations of the data can be identified.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife