Cancer Biology

GCN2 eIF2 kinase promotes prostate cancer by maintaining amino acid homeostasis

1. Ricardo A Cordova
2. Jagannath Misra
3. Parth H Amin
4. Anglea J Klunk
5. Nur P Damayanti
6. Kenneth R Carlson
7. Andrew J Elmendorf
8. Hyeong-Geug Kim
9. Emily T Mirek
10. Bennet D Elzey
11. Marcus J Miller
12. X Charlie Dong
13. Liang Cheng
14. Tracy G Anthony
15. Roberto Pili
16. Ronald C Wek
17. Kirk A Staschke

• Curated by eLife

  Evaluation Summary:

  This manuscript is an important body of work that addresses the role of the integrated stress response (ISR) and the role of the GCN2 protein kinase in prostate cancer. The studies comprehensively elucidate how GCN2 and amino acid transporters and uptake promote prostate cancer proliferation, as well as the therapeutic potential of inhibiting this pathway. This work, therefore, provides insights for both identification of new mechanisms and experimental therapeutics in prostate 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 #2 agreed to share their name with the authors.)

Reviewed by eLife

Nuclear fascin regulates cancer cell survival

1. Campbell D Lawson
2. Samantha Peel
3. Asier Jayo
4. Adam Corrigan
5. Preeti Iyer
6. Mabel Baxter Dalrymple
7. Richard J Marsh
8. Susan Cox
9. Isabel Van Audenhove
10. Jan Gettemans
11. Maddy Parsons

• Curated by eLife

  Evaluation Summary:

  This work explores a topic of high interest to cell and cancer biologists - the role of actin polymerization, and here specifically the role of fascin, in the nucleus. The authors show that fascin regulates nuclear actin, chromatin organization, response to DNA damage, and demonstrate the need for control of steady-state nuclear levels to avoid cell death. Studying nuclear actin is technically challenging, and the authors deploy some novel technologies towards this goal. There are some very elegant experiments in this paper that suggest fascin has an important role in regulating nuclear actin and other important aspects of cancer cell behaviour. The work could be enhanced by the authors considering adding some additional experiments and providing clarifications and some further details or discussion.

  (This preprint has been reviewed by eLife. We include the joint public review from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. All three Reviewers agreed to share their names with the authors.)

Reviewed by eLife

The “LINC” between Δ40p53-miRNA Axis in the Regulation of Cellular Homeostasis

1. Apala Pal
2. Pritam Kumar Ghosh
3. Saumitra Das

Reviewed by Review Commons

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-22-3p 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