Cancer Biology

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

DuoHexaBody-CD37 induces direct cytotoxic signaling in diffuse large B-cell lymphoma

1. Simar Pal Singh
2. Michelle D van den Beukel
3. Sjoerd van Deventer
4. Marije B Overdijk
5. M Guy Roukens
6. Kim CM Santegoets
7. Esther CW Breij
8. Martin ter Beest
9. Annemiek B van Spriel

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding on the direct cytotoxic effects of DuoHexaBody-CD37 in diffuse large B-cell lymphoma, mediated via SHP-1 activation and antibody clustering, independent of complement. The evidence supporting this mechanism is incomplete, with additional work needed to clarify SHP-1's role, the contribution of Fc receptor crosslinking, and the biological relevance across normal and malignant B cells. As the findings are based primarily on in vitro models, further validation would be required to support broader translational conclusions.

Reviewed by eLife

RUNX2 isoform II protects cancer cells from ferroptosis and apoptosis by promoting PRDX2 expression in oral squamous cell carcinoma

1. Junjun Huang
2. Rong Jia
3. Jihua Guo

• Curated by eLife

  eLife Assessment

  This paper investigates how isoform II of transcription factor RUNX2 promotes cell survival and proliferation in oral squamous cell carcinoma cell lines. The authors used gain and loss of function techniques to provide convincing evidence showing that RUNX2 isoform silencing led to cell death via several mechanisms including apoptosis and ferroptosis that was partially suppressed through RUNX2 regulation of PRDX2 expression. The study provides valuable insight into the underlying mechanism by which RUNX2 acts in oral squamous cell carcinoma.

Reviewed by eLife

Δ133p53α and Δ160p53α isoforms of the tumor suppressor protein p53 exert dominant-negative effect primarily by co-aggregation

1. Liuqun Zhao
2. Tanel Punga
3. Suparna Sanyal

• Curated by eLife

  eLife Assessment

  This important study investigates the molecular mechanisms by which the p53 isoforms Δ133p53α and Δ160p53α exert dominant-negative effects on full-length p53 (FLp53). Through a combination of chromatin immunoprecipitation, transcriptional reporter assays, subcellular localization analyses, and protein aggregation experiments, the authors provide solid evidence that these N-terminally truncated isoforms promote co-aggregation with FLp53, disrupting its transcriptional activity and cellular distribution. The revised manuscript successfully addresses prior reviewer concerns, and the findings are well supported by the experimental data.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife, Review Commons