Cancer Biology

Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations

1. Gaurav S Choudhary
2. Andrea Pellagatti
3. Bogos Agianian
4. Molly A Smith
5. Tushar D Bhagat
6. Shanisha Gordon-Mitchell
7. Srabani Sahu
8. Sanjay Pandey
9. Nishi Shah
10. Srinivas Aluri
11. Ritesh Aggarwal
12. Sarah Aminov
13. Leya Schwartz
14. Violetta Steeples
15. Robert N Booher
16. Murali Ramachandra
17. Maria Samson
18. Milagros Carbajal
19. Kith Pradhan
20. Teresa V Bowman
21. Manoj M Pillai
22. Britta Will
23. Amittha Wickrema
24. Aditi Shastri
25. Robert K Bradley
26. Robert E Martell
27. Ulrich G Steidl
28. Evripidis Gavathiotis
29. Jacqueline Boultwood
30. Daniel T Starczynowski
31. Amit Verma

• Curated by eLife

  Evaluation Summary:

  This is an outstanding manuscript evaluating a mutation commonly seen in AML and MDS in a spliceosome protein called SF3B1. The authors link this spliceosome mutation to altered transcripts and ultimately to cell cycle proteins and differentiation. This paper will be of high interest for oncologists in that it demonstrates that AML and MDS cells with this mutation can be targeted in a precision medicine approach.

  (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

Inhibition of mutant RAS-RAF interaction by mimicking structural and dynamic properties of phosphorylated RAS

1. Metehan Ilter
2. Ramazan Kasmer
3. Farzaneh Jalalypour
4. Canan Atilgan
5. Ozan Topcu
6. Nihal Karakas
7. Ozge Sensoy

• Curated by eLife

  Evaluation Summary:

  This is potentially an interesting paper in which extensive MD simulations are used to probe the effect of phosphorylation of a tyrosine residue on the conformational ensemble of Ras GTPase. The insights form the basis for a screen of small molecule(s) that disrupt interaction with its target Raf kinase, and predictions are tested experimentally. Overall, the integrated approach is of interest to a wide range of biochemist and protein scientists and could potentially be used to modulate the activities of other proteins.

  (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

Arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase

1. Ning Yang
2. Xuebo Lu
3. Yanan Jiang
4. Lili Zhao
5. Donghao Wang
6. Yaxing Wei
7. Yin Yu
8. Myoung Ok Kim
9. Kyle Vaughn Laster
10. Xin Li
11. Baoyin Yuan
12. Zigang Dong
13. Kangdong Liu

• Curated by eLife

  Evaluation Summary:

  This manuscript will be of interest to a broad audience of cancer biologists, especially those interested in esophageal cancer or treatment strategies involving ATR inhibition. It provides novel information about how FDA-approved antiretroviral compound Arbidol is a potential ATR inhibitor, which is of interest in the treatment of multiple tumor types. The key claims of the manuscript are supported by in silico, in vitro, and in vivo data.

  (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

Response to immune checkpoint blockade improved in pre-clinical model of breast cancer after bariatric surgery

1. Laura M Sipe
2. Mehdi Chaib
3. Emily B Korba
4. Heejoon Jo
5. Mary Camille Lovely
6. Brittany R Counts
7. Ubaid Tanveer
8. Jeremiah R Holt
9. Jared C Clements
10. Neena A John
11. Deidre Daria
12. Tony N Marion
13. Margaret S Bohm
14. Radhika Sekhri
15. Ajeeth K Pingili
16. Bin Teng
17. James A Carson
18. D Neil Hayes
19. Matthew J Davis
20. Katherine L Cook
21. Joseph F Pierre
22. Liza Makowski

• Curated by eLife

  Evaluation Summary:

  This study investigates on how weight loss by bariatric surgery or weight-matched dietary intervention impairs breast cancer growth as well as immunotherapy. This study can potentially provide some therapeutic intervention strategies on combining vertical sleeve gastrectomy and immunotherapy in treating breast 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

GPR183 mediates the capacity of the novel CD47-CD19 bispecific antibody TG-1801 to heighten ublituximab-umbralisib (U2) anti-lymphoma activity

1. Marcelo Lima Ribeiro
2. Núria Profitós-Pelejà
3. Juliana Carvalho Santos
4. Pedro Blecua
5. Diana Reyes Garau
6. Marc Armengol
7. Miranda Fernández-Serrano
8. Hari P. Miskin
9. Francesc Bosch
10. Manel Esteller
11. Emmanuel Normant
12. Gael Roué

• Curated by eLife

  Evaluation Summary:

  Ribeiro M et al investigate the ability of a novel bispecific CD19-CD47 antibody to enhance the cell mediated killing mediated by existing drug combinations - anti-CD20 plus PIK3d/CK1E inhibitor. The novelty of this study is the restriction to CD19 positive lymphoma cells, thus potentially avoiding toxicity to non-lymphoma lineages, and the gene expression profiling to identify up regulation of GPR183 after combined treatment of CD19/47 plus CD20/PI3K/CK1E vs CD19/47 alone. Genetic and drug studies suggest that GPR183 is essential for the full activity of the triplet drug combination.

  (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

Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation

1. Wesley L Cai
2. Jocelyn Fang-Yi Chen
3. Huacui Chen
4. Emily Wingrove
5. Sarah J Kurley
6. Lok Hei Chan
7. Meiling Zhang
8. Anna Arnal-Estape
9. Minghui Zhao
10. Amer Balabaki
11. Wenxue Li
12. Xufen Yu
13. Ethan D Krop
14. Yali Dou
15. Yansheng Liu
16. Jian Jin
17. Thomas F Westbrook
18. Don X Nguyen
19. Qin Yan

• Curated by eLife

  Evaluation Summary:

  The authors of this manuscript, which is of interest to the cancer community, identify the chromatin regulator WDR5 as a possible new drug target in triple negative breast cancer. Targeted therapeutics for this patient population are of high scientific and clinical interest, and the authors provide a compelling case that co-targeting WDR5 along with mTOR provides a promising new therapeutic strategy.

  (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

Inducible lncRNA transgenic mice reveal continual role of HOTAIR in promoting breast cancer metastasis

1. Qing Ma
2. Liuyi Yang
3. Karen Tolentino
4. Guiping Wang
5. Yang Zhao
6. Ulrike M Litzenburger
7. Quanming Shi
8. Lin Zhu
9. Chen Yang
10. Huiyuan Jiao
11. Feng Zhang
12. Rui Li
13. Miao-Chih Tsai
14. Jun-An Chen
15. Ian Lai
16. Hong Zeng
17. Lingjie Li
18. Howard Y Chang

• Curated by eLife

  Evaluation Summary:

  The long non-coding RNA HOTAIR has been widely reported to be overexpressed in many cancers, including breast cancer, and is strongly associated with disease progression and poor patient outcomes. A valuable new mouse model was developed for studying the functional effects of overexpressing HOTAIR and the mechanism of action of HOTAIR and used to demonstrate overexpression of HOTAIR promoted breast cancer metastasis to the lung. The mouse model and the conclusions will be of interest to researchers interested in improving treatment for breast 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 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Confined migration promotes cancer metastasis through resistance to anoikis and increased invasiveness

1. Deborah Fanfone
2. Zhichong Wu
3. Jade Mammi
4. Kevin Berthenet
5. David Neves
6. Kathrin Weber
7. Andrea Halaburkova
8. François Virard
9. Félix Bunel
10. Catherine Jamard
11. Hector Hernandez-Vargas
12. Stephen WG Tait
13. Ana Hennino
14. Gabriel Ichim

• Curated by eLife

  Evaluation Summary:

  The study proposes that confined migration renders breast cancer cells resistant to apoptosis via NFkappaB-dependent mechanisms. The technical aspects of the study are impressive and experiments are very well performed and demonstrate the value of mimetic bioengineering approaches, but the postulated central premise would require more rigorous support.

  (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 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Differentiated glioma cell-derived fibromodulin activates integrin-dependent Notch signaling in endothelial cells to promote tumor angiogenesis and growth

1. Shreoshi Sengupta
2. Mainak Mondal
3. Kaval Reddy Prasasvi
4. Arani Mukherjee
5. Prerna Magod
6. Serge Urbach
7. Dinorah Friedmann-Morvinski
8. Philippe Marin
9. Kumaravel Somasundaram

• Curated by eLife

  Evaluation Summary:

  The authors shed light on the role that non-cancer stem cell exerts in promoting cancer progression, revealing that non-cancer stem cell-secreted fibromodulin is crucial in mediating angiogenesis in glioma via integrin-dependent Notch signaling. The logic is smooth and clear and the results are solid, and the findings should be interesting for those who are expertized in the field of cancer biology and cancer stem cell.

  (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 name with the authors.)

Reviewed by eLife

Continuous sensing of IFNα by hepatic endothelial cells shapes a vascular antimetastatic barrier

1. Ngoc Lan Tran
2. Lorena Maria Ferreira
3. Blanca Alvarez-Moya
4. Valentina Buttiglione
5. Barbara Ferrini
6. Paola Zordan
7. Andrea Monestiroli
8. Claudio Fagioli
9. Eugenia Bezzecchi
10. Giulia Maria Scotti
11. Antonio Esposito
12. Riccardo Leone
13. Chiara Gnasso
14. Andrea Brendolan
15. Luca G Guidotti
16. Giovanni Sitia

Reviewed by Review Commons