Cancer Biology

Aspirin’s effect on kinetic parameters of cells contributes to its role in reducing incidence of advanced colorectal adenomas, shown by a multiscale computational study

1. Yifan Wang
2. C Richard Boland
3. Ajay Goel
4. Dominik Wodarz
5. Natalia L Komarova

• Curated by eLife

  Evaluation Summary:

  This work develops a multistage/component mathematical model to analyze advanced colorectal adenomas and the impact that aspirin therapy has on adenoma formation rates. This study will be interesting to the cancer evolution community and in particular those interested in colorectal cancer incidence. While the model is mainly focused on aspirin chemoprevention, the model could be adapted to test other putative preventative agents, and thus could have a broad impact.

  (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 names with the authors.)

Reviewed by eLife

Blockade of the pro‐fibrotic reaction mediated by the miR‐143/‐145 cluster enhances the responses to targeted therapy in melanoma

1. Serena Diazzi
2. Alberto Baeri
3. Julien Fassy
4. Margaux Lecacheur
5. Oskar Marin‐Bejar
6. Christophe A Girard
7. Lauren Lefevre
8. Caroline Lacoux
9. Marie Irondelle
10. Carine Mounier
11. Marin Truchi
12. Marie Couralet
13. Mickael Ohanna
14. Alexandrine Carminati
15. Ilona Berestjuk
16. Frederic Larbret
17. David Gilot
18. Georges Vassaux
19. Jean‐Christophe Marine
20. Marcel Deckert
21. Bernard Mari
22. Sophie Tartare‐Deckert

Reviewed by Review Commons

ZHX2 promotes HIF1α oncogenic signaling in triple-negative breast cancer

1. Wentong Fang
2. Chengheng Liao
3. Rachel Shi
4. Jeremy M Simon
5. Travis S Ptacek
6. Giada Zurlo
7. Youqiong Ye
8. Leng Han
9. Cheng Fan
10. Lei Bao
11. Christopher Llynard Ortiz
12. Hong-Rui Lin
13. Ujjawal Manocha
14. Weibo Luo
15. Yan Peng
16. William Y Kim
17. Lee-Wei Yang
18. Qing Zhang

• Curated by eLife

  Evaluation Summary:

  This study identifies ZHX2 as an oncogenic factor in triple negative breast cancer (TNBC), which interferes with hypoxia-related regulators and accounts for cancer aggressiveness and poor prognosis. The authors show that ZHX2 interacts with HIF1α and increases the expression of its downstream targets and identify ZHX2 residues critical for regulating its activity. This work provides a potential novel target in TNBC treatment and would be of interest to cancer biology researchers.

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

Reviewed by eLife

Metabolic requirement for GOT2 in pancreatic cancer depends on environmental context

1. Samuel A Kerk
2. Lin Lin
3. Amy L Myers
4. Damien J Sutton
5. Anthony Andren
6. Peter Sajjakulnukit
7. Li Zhang
8. Yaqing Zhang
9. Jennifer A Jiménez
10. Barbara S Nelson
11. Brandon Chen
12. Anthony Robinson
13. Galloway Thurston
14. Samantha B Kemp
15. Nina G Steele
16. Megan T Hoffman
17. Hui-Ju Wen
18. Daniel Long
19. Sarah E Ackenhusen
20. Johanna Ramos
21. Xiaohua Gao
22. Zeribe C Nwosu
23. Stefanie Galban
24. Christopher J Halbrook
25. David B Lombard
26. David R Piwnica-Worms
27. Haoqiang Ying
28. Marina Pasca di Magliano
29. Howard C Crawford
30. Yatrik M Shah
31. Costas A Lyssiotis

• Curated by eLife

  Evaluation Summary:

  This paper investigating specific metabolic dependencies of pancreatic cancer cells growing in vitro and in vivo will be of interest to scientists in the field of cancer metabolism. The data reveal that cancer-associated stromal cells can play an important role supporting the redox state of cancer cells cultured in vitro, but at present the data do not support the conclusion that this mechanism controls the metabolic resilience of cancer cells growing in vivo and alternate hypotheses remain to be addressed.

  (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

SARS-CoV-2 triggers DNA damage response in Vero E6 cells

1. Joshua Victor
2. Jamie Deutsch
3. Annalis Whitaker
4. Erica N. Lamkin
5. Anthony March
6. Pei Zhou
7. Jason W. Botten
8. Nimrat Chatterjee

Reviewed by ScreenIT

Transferred mitochondria accumulate reactive oxygen species, promoting proliferation

1. Chelsea U Kidwell
2. Joseph R Casalini
3. Soorya Pradeep
4. Sandra D Scherer
5. Daniel Greiner
6. Defne Bayik
7. Dionysios C Watson
8. Gregory S Olson
9. Justin D Lathia
10. Jarrod S Johnson
11. Jared Rutter
12. Alana L Welm
13. Thomas A Zangle
14. Minna Roh-Johnson

• Curated by eLife

  eLife assessment

  This manuscript provides compelling evidence that macrophages transfer mitochondria to cancer cells and that transferred mitochondria stimulate proliferation in recipient cells. The usage an array of clever cell biology-based tools provides compelling evidence for these claims despite the difficulties associated with studying a relatively low probability event. Solid evidence supports the proposed model that transferred mitochondria induce proliferation by stimulating ERK signaling in a ROS dependent manner, although at present some aspects of the proposed model are incomplete. The work has broad significance for both mitochondrial biology and cancer biology as the authors show clear evidence of mitochondrial transfer in mouse models of human tumors.

Reviewed by eLife, ASAPbio crowd review

A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines

1. Sara Feola
2. Jacopo Chiaro
3. Beatriz Martins
4. Salvatore Russo
5. Manlio Fusciello
6. Erkko Ylösmäki
7. Chiara Bonini
8. Eliana Ruggiero
9. Firas Hamdan
10. Michaela Feodoroff
11. Gabriella Antignani
12. Tapani Viitala
13. Sari Pesonen
14. Mikaela Grönholm
15. Rui MM Branca
16. Janne Lehtiö
17. Vincenzo Cerullo

• Curated by eLife

  Evaluation Summary:

  This study describes an immunopeptidomic-based pipeline to discover new tumor antigens for the development of cancer vaccines. The pipeline is relatively straightforward and exploits molecular mimicry and tumor pathogen cross-reactive T-cells and would be interesting for cancer immunologists. If the utility of the pipeline were demonstrated in more diverse systems, including carcinogen-induced tumors and human settings, this work would provide an immediate impact to the immuno-oncology field and personalized cancer vaccine development.

  (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

HBO1-MLL interaction promotes AF4/ENL/P-TEFb-mediated leukemogenesis

1. Satoshi Takahashi
2. Akinori Kanai
3. Hiroshi Okuda
4. Ryo Miyamoto
5. Yosuke Komata
6. Takeshi Kawamura
7. Hirotaka Matsui
8. Toshiya Inaba
9. Akifumi Takaori-Kondo
10. Akihiko Yokoyama

• Curated by eLife

  Evaluation Summary:

  This manuscript describes the identification and characterization of the interaction between MLL fusion proteins with the HBO1 histone acetyltransferase complex and its role in leukemogenesis. This study adds mechanistic depth into the important recent discovery of HBO1 functions in MLL-fusion leukemias and opens possibilities for a new therapeutic 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 #1 agreed to share their name with the authors.)

Reviewed by eLife

The tumor-suppressive long noncoding RNA DRAIC inhibits protein translation and induces autophagy by activating AMPK

1. Shekhar Saha
2. Ying Zhang
3. Briana Wilson
4. Roger Abounader
5. Anindya Dutta

Reviewed by Review Commons

Oncogenic PKA signaling increases c-MYC protein expression through multiple targetable mechanisms

1. Gary KL Chan
2. Samantha Maisel
3. Yeonjoo C Hwang
4. Bryan C Pascual
5. Rebecca RB Wolber
6. Phuong Vu
7. Krushna C Patra
8. Mehdi Bouhaddou
9. Heidi L Kenerson
10. Huat C Lim
11. Donald Long
12. Raymond S Yeung
13. Praveen Sethupathy
14. Danielle L Swaney
15. Nevan J Krogan
16. Rigney E Turnham
17. Kimberly J Riehle
18. John D Scott
19. Nabeel Bardeesy
20. John D Gordan

• Curated by eLife

  Evaluation Summary:

  In this article, global kinome profiling using fibrolamellar carcinoma and melanoma cell line models was employed to identify key effectors of protein kinase A (PKA) oncogenic signaling, which is hyperactivated in these cancer types. Based on use of molecular and cellular biology assays, authors proposed a model whereby the oncogenic effects of PKA are at least in part mediated by Aurora Kinase A (AURKA)- and PIM2-dependent regulation of MYC family members, and provide evidence that cancers with constitutive activation of PKA may be sensitive to AURKA inhibitors. Overall, it was thought that this study is of broad interest inasmuch as it provides new insights into the molecular underpinnings of oncogenic PKA signaling, and suggests the potential of using AURKA inhibitors to target malignancies characterized by aberrant PKA activation. With stronger mechanistic data linking constitutive PKA signaling to activation of AURKA and PIM2 and MYC regulation and in vivo experiments to support the conclusions, this manuscript will be of interest to researchers in the fields of cancer research, therapeutics, signal transduction and molecular and cell biology.

  (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