Cancer Biology

Mitochondrial ETF insufficiency drives neoplastic growth by selectively optimizing cancer bioenergetics

1. David Papadopoli
2. Ranveer Palia
3. Predrag Jovanovic
4. Sébastien Tabariès
5. Emma Ciccolini
6. Valerie Sabourin
7. Sebastian Igelmann
8. Shannon McLaughlan
9. Lesley Zhan
10. HaEun Kim
11. Nabila Chekkal
12. Krzysztof J Szkop
13. Thierry Bertomeu
14. Jibin Zeng
15. Julia Vassalakis
16. Farzaneh Afzali
17. Slim Mzoughi
18. Ernesto Guccione
19. Mike Tyers
20. Daina Avizonis
21. Ola Larsson
22. Lynne-Marie Postovit
23. Sergej Djuranovic
24. Josie Ursini-Siegel
25. Peter M Siegel
26. Michael Pollak
27. Ivan Topisirovic

• Curated by eLife

  eLife Assessment

  The authors present an important set of data implicating ETFDH as an epigenetically suppressed gene in cancer with tumor suppressive functions. The evidence is solid, with the authors demonstrating that ETFDH suppression results in accumulation of amino acids that impact metabolism via hyperactive mTORC1.

Reviewed by eLife

Repression of the Wnt pathway effector TCF7L2 reverses lethal cachexia in mice with intestinal cancers

1. Mei Ling Leong
2. Christiane Ruedl
3. Klaus Karjalainen

• Curated by eLife

  eLife Assessment

  In this valuable study, the authors demonstrate that TCF7L2 plays a role in the pathogenesis of cachexia in a mouse model of GI cancer. The results are solid, although future studies will need further mechanistic analyses. These data will be interesting to cancer biologists, especially those trying to understand late-stage complications such as cachexia and wasting, a major cause of cancer morbidity and mortality.

Reviewed by eLife

Human RAP2A Homolog of the Drosophila Asymmetric Cell Division Regulator Rap2l Targets the Stemness of Glioblastoma Stem Cells

1. Maribel Franco
2. Ricardo Gargini
3. Víctor M Barberá
4. Miguel Saceda
5. Ana Carmena

• Curated by eLife

  eLife Assessment

  This useful study explores the role of RAP2A in asymmetric cell division (ACD) regulation in glioblastoma stem cells (GSCs), drawing parallels to Drosophila ACD mechanisms and proposing that an imbalance toward symmetric divisions drives tumor progression. While findings on RAP2A's role in GSC expansion are promising, the study is nevertheless incomplete. Limitations include the lack of comprehensive GBM subtype analysis, insufficient mechanistic validation, and reliance on neurosphere models without in vivo confirmation. Addressing those gaps is necessary to substantiate the study's claims.

Reviewed by eLife

Defined cellular reprogramming of androgen receptor-active prostate cancer to neuroendocrine prostate cancer

1. Shan Li
2. Kai Song
3. Huiyun Sun
4. Yong Tao
5. Arthur Huang
6. Vipul Bhatia
7. Brian Hanratty
8. Radhika A Patel
9. Henry W Long
10. Colm Morrissey
11. Michael C Haffner
12. Peter S Nelson
13. Thomas G Graeber
14. John K Lee

• Curated by eLife

  eLife Assessment

  The study by Li et al. provides fundamental findings supported by convincing evidence that they defined cellular reprogramming of androgen receptor in neuroendocrine prostate cancer (NEPC). The findings enhance the understanding of the treatment of androgen receptor functions in NEPC.

Reviewed by eLife

Tumor Cell Spatial Organization Directs EGFR/RAS/RAF Pathway Primary Therapy Resistance through YAP Signaling

1. Rachel Nakagawa
2. Andrew Beardsley
3. Sophia Durney
4. Mary-Kate Hayward
5. Vishvak Subramanyam
6. Nathaniel P Meyer
7. Harrison Wismer
8. Hani Goodarzi
9. Valerie M Weaver
10. Daniel Van de Mark
11. Andrei Goga

• Curated by eLife

  eLife Assessment

  This study identifies a role for YAP in regulating tumor cell growth and drug response with differential effects noted based upon growth conditions in monolayer vs spheroid culture. This work has the potential to define more biologically relevant cell culture model systems for drug resistance and define targetable pathways to overcome drug resistance. The findings described are important to the cancer biology field and the evidence supporting the key findings is convincing.

Reviewed by eLife

Targeting de novo cholesterol synthesis in rhabdomyosarcoma induces cell cycle arrest and triggers apoptosis through ER stress-mediated pathways

1. Nebeyu Yosef Gizaw
2. Kalle Kolari
3. Kari Alitalo
4. Riikka Kivelä

Reviewed by Review Commons

KDM5 demethylases suppress R-loop-mediated “viral mimicry” and DNA damage in breast cancer cells

1. Lena Lau
2. Kurt Henderson
3. Ahu Turkoz
4. Sara Linker
5. Dörte Schlesinger
6. Brad Townsley
7. Brian Egan
8. Shoba Ragunathan
9. Robert Rollins
10. Xianju Bi
11. Zhijian Chen
12. Oleg Brodsky
13. Clifford Restaino
14. Murali Gururajan
15. Kristen Jensen-Pergakes
16. Anders Malarstig
17. Chames Kermi
18. Paul Moore
19. Marie Classon

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding that KDM5 inhibition activates the interferon response and antigen presentation genes in breast cancer cells through R-loops. The evidence supporting the claims of the authors is solid, although the inclusion of further in vivo studies displaying the effects of KDM5 inhibitors on the immunotherapy responses of breast tumors would have strengthened the study. The work will be of interest to scientists working in the field of breast cancer immunotherapy.

Reviewed by eLife

Microenvironmental arginine restriction sensitizes pancreatic cancers to polyunsaturated fatty acids by suppression of lipid synthesis

1. Patrick B Jonker
2. Mumina Sadullozoda
3. Guillaume Cognet
4. Juan J Apiz Saab
5. Kelly H Sokol
6. Violet X Wu
7. Deepa Kumari
8. Colin Sheehan
9. Mete E Ozgurses
10. Darby Agovino
11. Grace Croley
12. Smit A Patel
13. Althea Bock-Hughes
14. Kay F Macleod
15. Hardik Shah
16. Jonathan L Coloff
17. Evan C Lien
18. Alexander Muir

• Curated by eLife

  eLife Assessment

  This important study shows that nutrient stress emanating from the microenvironment induces metabolic vulnerabilities in pancreatic ductal adenocarcinoma (PDAC). Using a combination of cell-based and mouse models, the authors provide compelling evidence showing that arginine restriction in the microenvironment disrupts lipid homeostasis in PDAC, resulting in the induction of ferroptosis upon exposure of tumors to polyunsaturated fatty acids. This report is likely to be of broad interest to researchers interested in studying cancer biology, tumor microenvironment, metabolism, and stress adaptation mechanisms.

Reviewed by eLife

A single cysteine residue in vimentin regulates long non-coding RNA XIST to suppress epithelial-mesenchymal transition and stemness in breast cancer

1. Saima Usman
2. W Andrew Yeudall
3. Muy-Teck Teh
4. Fatemah Ghloum
5. Hemanth Tummala
6. Ahmad Waseem

• Curated by eLife

  eLife Assessment

  This valuable study reveals that the structural protein vimentin promotes the epithelial-mesenchymal transition in breast cancer cells. Utilizing robust and validated methodologies, the data collected provide a solid foundation for further investigation into metastasis models. This work will be of significant interest to researchers in the field of breast cancer.

Reviewed by eLife

Targeting SLC7A11-mediated cysteine metabolism for the treatment of trastuzumab-resistant HER2-positive breast cancer

1. Yijia Hua
2. Ningjun Duan
3. Chunxiao Sun
4. Fan Yang
5. Min Tian
6. Yanting Sun
7. Shuhan Zhao
8. Jue Gong
9. Qian Liu
10. Xiang Huang
11. Yan Liang
12. Ziyi Fu
13. Wei Li
14. Yongmei Yin

• Curated by eLife

  eLife Assessment

  This study provides compelling evidence that SLC7A11 may serve as a potential therapeutic target for trastuzumab-resistant HER2-positive breast cancer. While the findings are well-supported by robust data, the study could have been further strengthened by incorporating additional cell line experiments and providing more detailed clarification on patient sample selection. Nevertheless, this valuable work represents a significant contribution and will be of considerable interest to researchers in the field of breast cancer.

Reviewed by eLife