Cancer Biology

The role of ATP synthase subunit e (ATP5I) in mediating the metabolic and antiproliferative effects of metformin in cancer cells

1. Guillaume Lefrançois
2. Emilie Lavallée
3. Marie-Camille Rowell
4. Véronique Bourdeau
5. Farzaneh Mohebali
6. Thierry Bertomeu
7. Ana Maria Duman
8. Maya Nikolova
9. Mike Tyers
10. Simon-Pierre Gravel
11. Andreea R Schmitzer
12. Gerardo Ferbeyre

• Curated by eLife

  eLife Assessment

  This valuable manuscript describes ATP5I, a subunit of F1Fo-ATP synthase, as a key target of medicinal biguanides. The knockout of ATP5I in pancreatic cancer cells mimics biguanide treatment, inducing a metabolic switch from OXPHOS to glycolysis due to a compromised expression of the Complex I protein NDUFB8. This results in a markedly decreased NAD/NADH ratio and decreased cell proliferation. These solid findings point out ATP5I as a promising mitochondrial target for cancer therapies and contribute to our understanding of metformin's mechanism of action since many of its molecular mechanisms remain poorly understood.

Reviewed by eLife

Integrated Human Transcriptomics Identifies Fallopian Tube Progenitors as Plausible Precursors of High-Grade Serous Ovarian Cancer

1. Qian Li
2. Keren Cheng
3. Lili Sun
4. Wei Yan

• Curated by eLife

  eLife Assessment

  This valuable study reports a substantial single-cell RNAseq and bulk RNAseq dataset from multiple high-grade serous ovarian cancers, including a single-cell atlas of human fallopian tube epithelium. The bioinformatic analysis investigating the lineage and location of epithelial progenitor cells is convincing, although this will require experimental validation. The work also provides a resource to examine additional features of normal fallopian tubes and ovarian cancers, and for developing methods for early detection and tumour stratification.

Reviewed by eLife

Acquired resistance to sotorasib in KRASG12C mutant NSCLC is vulnerable to PI3K-mTOR pathway inhibition mediated by 4E-BP1, a regulator of cap-dependent translation

1. Ismail M Meraz
2. Shuhong Wu
3. Yi Xu
4. Lihui Gao
5. Meng Feng
6. Chenghui Ren
7. Renduo Song
8. Ran Zhang
9. Qi Wang
10. Yuanxin Xi
11. Sung Yun Jung
12. Jing Wang
13. Bingliang Fang
14. Mourad Majidi
15. Jack A Roth

• Curated by eLife

  eLife Assessment

  The authors investigate mechanisms of acquired resistance (AR) to KRAS-G12C inhibitors (sotorasib) in non-small cell lung cancer, proposing that resistance arises from signaling rewiring rather than additional mutations. While the study addresses a valuable clinical question, it is limited by several weaknesses in experimental rigor, data interpretation, and presentation, meaning the strength of evidence is incomplete.

Reviewed by eLife

Design of combination therapeutics from protein response to drugs in ovarian cancer cells

1. Alexandra Franz
2. Ciyue Shen
3. Fabian Coscia
4. Kenneth Munroe
5. Lea Charaoui
6. Anil Korkut
7. Matthias Mann
8. Augustin Luna
9. Chris Sander

• Curated by eLife

  eLife Assessment

  In this important study, the authors provide a simple yet elegant approach to identifying therapeutic targets that synergize to prevent therapeutic resistance in ovarian cancer using cell lines, data-independent acquisition proteomics, and bioinformatic analysis. The authors convincingly identify several combinations of pharmaceuticals that were able to overcome or prevent therapeutic resistance in culture models of ovarian cancer, a disease with an unmet diagnostic and therapeutic need. This work will be of interest to researchers focused on ovarian cancer.

Reviewed by eLife

Caveolin-1 regulates context-dependent signaling and survival in Ewing sarcoma

1. Dagan Segal
2. Xiaoyu Wang
3. Hanieh Mazloom-Farisbaf
4. Felix Y. Zhou
5. Divya Rajendran
6. Erin Butler
7. Bingying Chen
8. Bo-Jui Chang
9. Khushi Ahuja
10. Averi Perny
11. Kushal Bhatt
12. Dana Kim Reed
13. Diego H. Castrillon
14. Jeon Lee
15. Elise Jeffery
16. Lei Wang
17. Khai Nguyen
18. Noelle S. Williams
19. Stephen X. Skapek
20. Satwik Rajaram
21. Reto Fiolka
22. Khuloud Jaqaman
23. Gary Hon
24. James F. Amatruda
25. Gaudenz Danuser

Reviewed by Review Commons

HER2-driven mammary tumorigenesis enhances bioenergetics despite reductions in mitochondrial content

1. Sara M Frangos
2. Henver S Brunetta
3. Dongdong Wang
4. Maria Joy Therese Jabile
5. Leslie M Jeffries
6. Grace Mencfeld
7. David WL Ma
8. William J Muller
9. Cezar M Khursigara
10. Kelsey H Fisher-Wellman
11. Jim Petrik
12. Gregory R Steinberg
13. Graham P Holloway

• Curated by eLife

  eLife Assessment

  This valuable study aims to determine mechanisms underlying breast cancer initiation and tumour progression. The manuscript includes a solid set of transcriptomic and proteomic datasets from tumour samples and examines mitochondrial function within the tumours. While the underlying mechanisms linking expression changes to functional effects remain speculative. This paper provides a resource for researchers working on breast cancer and/or HER2-driven bioenergetics changes.

Reviewed by eLife

Ancient and Animal-Specific Regulatory Modes of EWS::FLI1 Revealed by a Minimal Yeast Model

1. Diego Velázquez
2. Cristina Molnar
3. Jose Reina
4. Jaume Mora
5. Cayetano Gonzalez

Reviewed by Review Commons

A Transcriptional Signature of Metabolic-Immune Conflict Fails to Provide Independent Prognostic or Predictive Value in Melanoma

1. Islam Asal

Reviewed by PREreview

Cross-Species Transcriptomic Integration Reveals a MIRO1-Mediated Macrophage–T Cell Axis in Glioma

1. Zehui Du
2. Menghan Li
3. Brandon H. Bergsneider
4. Andy P. Tsai
5. Kwang Bog Cho
6. Lily H. Kim
7. John Choi
8. Gordon Li
9. Tony Wyss-Coray
10. Michael Lim
11. Xinnan Wang

Reviewed by Review Commons

Blocking SHP2 benefits FGFR2 inhibitor and overcomes its resistance in FGFR2-amplified gastric cancer

1. Yue Zhang
2. Hanbing Wang
3. Yutao Wei
4. Yunfeng Pan
5. Xueru Song
6. Jie Shao
7. Lixia Yu
8. Tao Shi
9. Yue Wang

• Curated by eLife

  eLife Assessment

  Based on the perceived low efficacy of current therapies targeted to FGFR2 in gastric cancer (GC), the authors investigate an approach which combines SHP2 inhibition with existing FGFR2 inhibitors. The data were largely collected and analysed using solid and validated methodology. There is some useful data regarding combination therapy in a new clinical cohort, which supports previous studies that have reported the potential of targeting RTKs together with phosphatases.

Reviewed by eLife