Cancer Biology

Therapeutic resistance in acute myeloid leukemia cells is mediated by a novel ATM/mTOR pathway regulating oxidative phosphorylation

1. Hae J Park
2. Mark A Gregory
3. Vadym Zaberezhnyy
4. Andrew Goodspeed
5. Craig T Jordan
6. Jeffrey S Kieft
7. James DeGregori

• Curated by eLife

  Evaluation Summary:

  FLT3 (Fms Related Receptor Tyrosine Kinase 3) activation occurs in a subset of acute myeloid leukemia (AML) cases and is associated with poor prognosis. This work is focused on the mechanisms of resistance to FLT3 inhibitors in AML. The authors show that the combination of the FLT3 inhibitor and an mTORC1 inhibitor reduces tumor burden and prevents relapse in FLT3 mutant AML. This paper is of interest in scientists and physicians investigating AML as well as scientists studying signaling pathways.

  (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

Cancer stem cell-derived extracellular vesicles preferentially target MHC-II–macrophages and PD1+ T cells in the tumor microenvironment

1. Patricia Gonzalez-Callejo
2. Zihan Guo
3. Tahereh Ziglari
4. Natalie Marcia Claudio
5. Kayla Hoang Nguyen
6. Naoki Oshimori
7. Joaquim Seras-Franzoso
8. Ferdinando Pucci

Reviewed by Review Commons

The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer

1. Daniel Routledge
2. Sally Rogers
3. Yosuke Ono
4. Lucy Brunt
5. Valerie Meniel
6. Giusy Tornillo
7. Hassan Ashktorab
8. Toby J Phesse
9. Steffen Scholpp

• Curated by eLife

  Evaluation Summary:

  The manuscript by Routledge et al. describes the role of Reggie-1/Flottilin2 in the formation of filopodia-like membrane protrusions called cytonemes and which were shown to be conserved between gastric cancer cells and Zebrafish. Authors demonstrate that Flot2 is present on the cytoneme along with Wnt3 in gastric cancer and with Wnt8a in Zebrafish. Furthermore, Flot2 is also present with Ror2 on the cytoneme and together they are believed to modulate cytoneme formation. This study extended the previous studies and provides new details about regulatory events controlling a cell biological process that will be of interest to those in the Wnt and cytoneme fields.

  (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

Suppression of endothelial miR-22 mediates non-small cell lung cancer cell-induced angiogenesis

1. Yuan Gu
2. Gianni Pais
3. Vivien Becker
4. Christina Körbel
5. Emmanuel Ampofo
6. Elke Ebert
7. Johannes Hohneck
8. Nicole Ludwig
9. Eckart Meese
10. Rainer M. Bohle
11. Yingjun Zhao
12. Michael D. Menger
13. Matthias W. Laschke

• Curated by eLife

  Evaluation Summary:

  This study reports a novel function of non-coding RNA miR-22 in the regulation of tumor-associated angiogenesis. The presented data suggest a possible link between microRNA and endothelial cell function. If the underlying mechanisms were further explored, this work would be interesting for people working on microRNA function in endothelial cells. Furthermore, considering the increasing interest of combination of anti-angiogenesis agents with anti-PD1 immunotherapy, this work may attract readers interested in immunology.

  (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

DNA methylome combined with chromosome cluster-oriented analysis provides an early signature for cutaneous melanoma aggressiveness

1. Arnaud Carrier
2. Cécile Desjobert
3. Loic Ponger
4. Laurence Lamant
5. Matias Bustos
6. Jorge Torres-Ferreira
7. Rui Henrique
8. Carmen Jeronimo
9. Luisa Lanfrancone
10. Audrey Delmas
11. Gilles Favre
12. Antoine Daunay
13. Florence Busato
14. Dave SB Hoon
15. Jorg Tost
16. Chantal Etievant
17. Joëlle Riond
18. Paola B Arimondo

• Curated by eLife

  Evaluation Summary:

  Predicting if a tumour has aggressive or metastatic characteristics would be of great utility in the clinic as it would help patient stratification and management. In this manuscript, Carrier and collaborators derive a signature for melanoma aggressiveness relying on methylated regions of tumour and cell line genomes. The identification of a 4-gene methylation biomarker for melanoma aggressiveness and survival is an important contribution. This manuscript is of relevance to clinicians and melanoma researchers interested in biomarker research.

  (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

Non-canonical miRNA-RNA base-pairing impedes tumor suppressor activity of miR-16

1. Anaïs M Quéméner
2. Laura Bachelot
3. Marc Aubry
4. Stéphane Avner
5. Delphine Leclerc
6. Gilles Salbert
7. Florian Cabillic
8. Didier Decaudin
9. Bernard Mari
10. Frédéric Mouriaux
11. Marie-Dominique Galibert
12. David Gilot

Reviewed by Review Commons

Defining cellular population dynamics at single-cell resolution during prostate cancer progression

1. Alexandre A Germanos
2. Sonali Arora
3. Ye Zheng
4. Erica T Goddard
5. Ilsa M Coleman
6. Anson T Ku
7. Scott Wilkinson
8. Hanbing Song
9. Nicholas J Brady
10. Robert A Amezquita
11. Michael Zager
12. Annalysa Long
13. Yu Chi Yang
14. Jason H Bielas
15. Raphael Gottardo
16. David S Rickman
17. Franklin W Huang
18. Cyrus M Ghajar
19. Peter S Nelson
20. Adam G Sowalsky
21. Manu Setty
22. Andrew C Hsieh

• Curated by eLife

  Evaluation Summary:

  Prostate cancer cellular heterogeneity is a major problem for disease progression and treatment resistance. This body of work addresses the cellular identity and populations that make up prostate cancer using single-cell sequencing technology and state-of-the-art mouse models. The cellular identities, associated signaling networks, and immune complexes accompanying the heterogeneity of the prostate are identified in this work and a resource is provided for scientists in the 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

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