Cancer Biology

Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance

1. Luca Tirinato
2. Maria Grazia Marafioti
3. Francesca Pagliari
4. Jeannette Jansen
5. Ilenia Aversa
6. Rachel Hanley
7. Clelia Nisticò
8. Daniel Garcia-Calderón
9. Geraldine Genard
10. Joana Filipa Guerreiro
11. Francesco Saverio Costanzo
12. Joao Seco

Reviewed by Review Commons

The novel, recurrent mutation in the TOP2A gene results in the enhanced topoisomerase activity and transcription deregulation in glioblastoma

1. Bartlomiej Gielniewski
2. Katarzyna Poleszak
3. Adria-Jaume Roura
4. Paulina Szadkowska
5. Sylwia K. Krol
6. Rafal Guzik
7. Paulina Wiechecka
8. Marta Maleszewska
9. Beata Kaza
10. Andrzej Marchel
11. Tomasz Czernicki
12. Andrzej Koziarski
13. Grzegorz Zielinski
14. Andrzej Styk
15. Maciej Kawecki
16. Cezary Szczylik
17. Ryszard Czepko
18. Mariusz Banach
19. Wojciech Kaspera
20. Wojciech Szopa
21. Mateusz Bujko
22. Bartosz Czapski
23. Miroslaw Zabek
24. Ewa Izycka-Swieszewska
25. Wojciech Kloc
26. Pawel Nauman
27. Joanna Cieslewicz
28. Bartosz Wojtas
29. Bozena Kaminska

Reviewed by Review Commons

Quantifying chromosomal instability from intratumoral karyotype diversity using agent-based modeling and Bayesian inference

1. Andrew R Lynch
2. Nicholas L Arp
3. Amber S Zhou
4. Beth A Weaver
5. Mark E Burkard

• Curated by eLife

  Evaluation Summary:

  This study seeks to develop a mathematical framework for estimating rates of chromosome missegregation based on known chromosomal properties and observed aneuploidy rates. A derived model is validated using live-cell imaging before being applied to several previously-described datasets from tumors and organoids. The subject matter is of high interest to aneuploidy and genome evolution 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

BRAFV600E induces reversible mitotic arrest in human melanocytes via microRNA-mediated suppression of AURKB

1. Andrew S McNeal
2. Rachel L Belote
3. Hanlin Zeng
4. Marcus Urquijo
5. Kendra Barker
6. Rodrigo Torres
7. Meghan Curtin
8. A Hunter Shain
9. Robert HI Andtbacka
10. Sheri Holmen
11. David H Lum
12. Timothy H McCalmont
13. Matt W VanBrocklin
14. Douglas Grossman
15. Maria L Wei
16. Ursula E Lang
17. Robert L Judson-Torres

• Curated by eLife

  Evaluation Summary:

  This interesting, timely and well-done study focuses on the mechanism underlying nevus growth arrest, which has received renewed attention as a result of recent studies that question the dogma that such arrest is mediated by oncogene-induced senescence. Through experiments involving both cultured primary human melanocytes and cells derived from clinical samples, the authors show that Braf-oncogene-induced nevus cell growth arrest results from microRNA-dependent suppression of the mitotic kinase Aurkb, which influences whether Braf activity is proliferative versus antiproliferative. While the conclusions made within the manuscript are justified, and there is sound acknowledgment of certain pitfalls that could be addressed in future research, more expansive sample sizes and further in vivo work would aid in providing more clinical relevance. This manuscript would appeal to researchers in the melanoma field, especially those studying the underlying mechanisms behind phenotypic plasticity and tumor heterogeneity.

  (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

Rpl24Bst mutation suppresses colorectal cancer by promoting eEF2 phosphorylation via eEF2K

1. John RP Knight
2. Nikola Vlahov
3. David M Gay
4. Rachel A Ridgway
5. William James Faller
6. Christopher Proud
7. Giovanna R Mallucci
8. Tobias von der Haar
9. Christopher Mark Smales
10. Anne E Willis
11. Owen J Sansom

• Curated by eLife

  Evaluation Summary:

  In this study, Knight and colleagues investigate the role of the ribosome and translational control in colorectal tumours. A mutation of a protein of the large ribosomal subunit, RPL24, is used to suppress tumours driven by two mutations found commonly in cancer, in APC and KRAS. The authors identify a mechanistic output of the RPL24 BST mutation, eEF2 phosphorylation, which they demonstrate is a major effector in inhibiting tumour cell translation and proliferation. By targeting the eEF2 kinase eEF2K, they restore protein synthesis in RPL24 mutant cells. The conclusion is well supported by the experimental data presented, which implies that translation elongation can be a potential therapeutic target of KRAS mutated CRC. Importantly, Rpl24Bst in wildtype intestine does not affect epithelial cell proliferation and differentiation, suggesting that translation elongation can be used as tumour-specific target.

  (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

HOXA9 promotes MYC-mediated leukemogenesis by maintaining gene expression for multiple anti-apoptotic pathways

1. Ryo Miyamoto
2. Akinori Kanai
3. Hiroshi Okuda
4. Yosuke Komata
5. Satoshi Takahashi
6. Hirotaka Matsui
7. Toshiya Inaba
8. Akihiko Yokoyama

• Curated by eLife

  Evaluation Summary:

  This manuscript is of potential interest to experimental haematologists studying initiation and maintenance factors in leukaemia. Overall, the study is well designed and the data is clearly presented. However, in some places the analysis lacks depth and technological sophistication, and the novel insights are limited without additional experimentation.

  (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

Effects of the COVID-19 pandemic on publication landscape in chimeric antigen receptor-modified immune cell research

1. Ahmet Yilmaz
2. Jianhua Yu

Reviewed by ScreenIT

Exosome component 1 cleaves single-stranded DNA and sensitizes kidney renal clear cell carcinoma cells to poly(ADP-ribose) polymerase inhibitor

1. Qi Xiao
2. Qiaoling Liu
3. Lina Wang
4. Na Wang
5. Kai Wang
6. Chengli Song
7. Qingkai Yang

• Curated by eLife

  Evaluation Summary:

  Targeting DNA repair pathway provides a novel approach managing malignancies and emphasizing the necessity of discovering biomarkers which could select patients who will benefit. In this research the authors performed comprehensive bioinformatic analysis and identified EXOSC1 as the endogenous source of mutation, which was then validated for its role in damaging DNA and could sensitize kidney renal clear cell carcinoma cells to DNA repair inhibitor. This research is innovative for proposing EXOSC1 role in mutagenesis and could serve as the biomarker to discriminate potential patients who would benefit from DNA repair inhibitor treatment.

  (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

Isoform-specific disruption of the TP73 gene reveals a critical role for TAp73γ in tumorigenesis via leptin

1. Xiangmudong Kong
2. Wensheng Yan
3. Wenqiang Sun
4. Yanhong Zhang
5. Hee Jung Yang
6. Mingyi Chen
7. Hongwu Chen
8. Ralph W de Vere White
9. Jin Zhang
10. Xinbin Chen

• Curated by eLife

  eLife assessment

  TP73 is a member of the p53 family of tumor suppressors. The authors provide compelling evidence that a TAp73-alpha to TAp73-gamma switch could be a frequent phenomenon in human cancers and provide novel evidence that TAp73-gamma has oncogenic functions via Leptin. The authors provide a substantial amount of high-quality data and convincingly demonstrate a novel function of this specific isoform of p73 in lipid metabolism and tumorigenesis.

Reviewed by eLife

Oxaliplatin resistance in colorectal cancer enhances TRAIL sensitivity via death receptor 4 upregulation and lipid raft localization

1. Joshua D Greenlee
2. Maria Lopez-Cavestany
3. Nerymar Ortiz-Otero
4. Kevin Liu
5. Tejas Subramanian
6. Burt Cagir
7. Michael R King

• Curated by eLife

  Evaluation Summary:

  The study investigates the molecular characteristics of chemotherapy-resistant colorectal cancer cells and proposes a therapeutic alternative for chemo-resistant cancer. The authors provide evidence in vitro that chemo-resistant cells are pro-apoptotic in the presence of the death receptor ligand TRAIL due to the enhanced localization of the death receptor DR4 in the lipid rafts of their plasma membrane. Based on this finding, the authors treat blood samples from 5 colorectal cancer patients with TRAIL-conjugated liposomes and observed reduction in the number of circulating cancer cells in the blood draws.

  (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