Cancer Biology

Type I and II PRMTs inversely regulate post-transcriptional intron detention through Sm and CHTOP methylation

1. Maxim I Maron
2. Alyssa D Casill
3. Varun Gupta
4. Jacob S Roth
5. Simone Sidoli
6. Charles C Query
7. Matthew J Gamble
8. David Shechter

• Curated by eLife

  Evaluation Summary:

  This manuscript addresses outstanding questions about the molecular mechanisms by which the two types of arginine-methylating enzymes affect the processing and fate of transcripts in mammalian cells. This work makes important inroads into these questions, uncovering an inverse effect of the two types of enzymes on intron retention during post-transcriptional splicing, linking the effects to specific target proteins. With better support of some key claims , the paper will provide a lot of new information about the functional consequences of asymmetric and symmetric demethylation.

  (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

Crosstalk with keratinocytes causes GNAQ oncogene specificity in melanoma

1. Oscar Urtatiz
2. Amanda Haage
3. Guy Tanentzapf
4. Catherine D Van Raamsdonk

• Curated by eLife

  Evaluation Summary:

  In this manuscript, the authors study the discrepancy between the frequency of mutations in Gq alpha subunit (GNAQ and its paralogue GNA11) in uveal vs cutaneous melanoma. They hypothesize that the restriction of GNAQ and GNA11 mutations to non-epithelial melanomas is due to epidermal factors, which convert the impact of GNAQ Q209L mutation from being oncogenic to being inhibitory to melanocyte survival and proliferation, and reduce the maintenance, rather than the establishment of interfollicular epithelial melanocytes. This work provides new insights into the poorly understood difference in mutation frequency in different melanoma types.

  (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

AR-V7 exhibits non-canonical mechanisms of nuclear import and chromatin engagement in castrate-resistant prostate cancer

1. Seaho Kim
2. CheukMan C Au
3. Mohd Azrin Bin Jamalruddin
4. Naira Essam Abou-Ghali
5. Eiman Mukhtar
6. Luigi Portella
7. Adeline Berger
8. Daniel Worroll
9. Prerna Vatsa
10. David S Rickman
11. David M Nanus
12. Paraskevi Giannakakou

• Curated by eLife

  Evaluation Summary:

  Truncated splice variants of the androgen receptor (AR) lacking a ligand-binding domain are thought to contribute to therapeutic resistance to antiandrogens in advanced prostate cancer. In this manuscript, the authors show that AR-V7, the most well-studied such truncated variant, displays a different mechanism of nuclear targeting and interaction with chromatin compared to the full-length AR. This work provides new insights into how AR-V7 may contribute to the pathology of Castrate-Resistant Prostate Cancer and will be of interest to researchers trying to improve prostate cancer therapies.

  (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

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