Cancer Biology

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

Genome-wide CRISPR screens identify novel regulators of wild-type and mutant p53 stability

1. YiQing Lü
2. Tiffany Cho
3. Saptaparna Mukherjee
4. Carmen Florencia Suarez
5. Nicolas S Gonzalez-Foutel
6. Ahmad Malik
7. Sebastien Martinez
8. Dzana Dervovic
9. Robin Hyunseo Oh
10. Ellen Langille
11. Khalid N Al-Zahrani
12. Lisa Hoeg
13. Zhen Yuan Lin
14. Ricky Tsai
15. Geraldine Mbamalu
16. Varda Rotter
17. Patricia Ashton-Prolla
18. Jason Moffat
19. Lucia Beatriz Chemes
20. Anne-Claude Gingras
21. Moshe Oren
22. Daniel Durocher
23. Daniel Schramek

Reviewed by Review Commons

Arginase 1 is a key driver of immune suppression in pancreatic cancer

1. Rosa E Menjivar
2. Zeribe C Nwosu
3. Wenting Du
4. Katelyn L Donahue
5. Hanna S Hong
6. Carlos Espinoza
7. Kristee Brown
8. Ashley Velez-Delgado
9. Wei Yan
10. Fatima Lima
11. Allison Bischoff
12. Padma Kadiyala
13. Daniel Salas-Escabillas
14. Howard C Crawford
15. Filip Bednar
16. Eileen Carpenter
17. Yaqing Zhang
18. Christopher J Halbrook
19. Costas A Lyssiotis
20. Marina Pasca di Magliano

• Curated by eLife

  Evaluation Summary:

  Menjivar et al. identify a previously unrecognized role of myeloid cell Arginase1 (Arg1) activity in shaping the anti-tumor immune response in pancreatic ductal adenocarcinoma (PDAC). The proposed therapeutic combination is a new approach for pancreatic cancer, with an enhanced response to immune therapy upon arginase inhibition.

  (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

Machine learning-assisted elucidation of CD81–CD44 interactions in promoting cancer stemness and extracellular vesicle integrity

1. Erika K Ramos
2. Chia-Feng Tsai
3. Yuzhi Jia
4. Yue Cao
5. Megan Manu
6. Rokana Taftaf
7. Andrew D Hoffmann
8. Lamiaa El-Shennawy
9. Marina A Gritsenko
10. Valery Adorno-Cruz
11. Emma J Schuster
12. David Scholten
13. Dhwani Patel
14. Xia Liu
15. Priyam Patel
16. Brian Wray
17. Youbin Zhang
18. Shanshan Zhang
19. Ronald J Moore
20. Jeremy V Mathews
21. Matthew J Schipma
22. Tao Liu
23. Valerie L Tokars
24. Massimo Cristofanilli
25. Tujin Shi
26. Yang Shen
27. Nurmaa K Dashzeveg
28. Huiping Liu

Reviewed by Review Commons