Cancer Biology

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. Lindsey N Dzierozynski
13. Chufan Cai
14. Leah M Ziolkowski
15. Smit A Patel
16. Althea Bock-Hughes
17. Kay F Macleod
18. Hardik Shah
19. Jonathan L Coloff
20. Evan C Lien
21. Alexander Muir

• Curated by eLife

  eLife Assessment

  This important study demonstrates that nutrient stress engenders metabolic vulnerabilities in pancreatic ductal adenocarcinoma (PDAC). By combining cell line and mouse models, the authors provide compelling evidence showing that arginine depletion from the microenvironment disrupts lipid homeostasis in PDAC resulting in 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, metabolic adaptations and stress responses.

Reviewed by eLife

Cancer cells differentially modulate mitochondrial respiration to alter redox state and enable biomass synthesis in nutrient-limited environments

1. Sarah M Chang
2. Muhammad Bin Munim
3. Sonia E Trojan
4. Huel Cox
5. Anna Shevzov-Zebrun
6. Keene L Abbott
7. Renee Chang
8. Matthew G Vander Heiden

• Curated by eLife

  eLife Assessment

  This study presents important findings on the relationship between nutrient availability and NAD/NADH levels, which in turn regulate biomass production in cancer cells. The authors provide convincing evidence to support their claims, offering insight into why it is difficult to predict which nutrients limit cancer cell growth: both cell type and nutrient availability together determine the oxidative capacity that constrains the synthesis of various metabolic intermediates. The manuscript will be of broad interest to researchers working in cancer and cell metabolism.

Reviewed by eLife

Restraint of melanoma progression by cells in the local skin environment

1. Yilun Ma
2. Mohita Tagore
3. Miranda V Hunter
4. Ting-Hsiang Huang
5. Emily Montal
6. Joshua M Weiss
7. Yingxiao Shi
8. Tuulia Vallius
9. Peter K Sorger
10. Richard M White

• Curated by eLife

  eLife Assessment

  In this important study, the authors used a zebrafish model and scRNAseq analysis to show that a subset of keratinocytes within melanoma microenvironment highly up-regulate Twist and undergo Epithelial-Mesenchymal Transition (EMT). Surprisingly, when overexpressing Twist in keratinocytes, the resulting alteration in keratinocytes is inhibitory for melanoma invasion in both zebrafish and human cell culture models. The results are supported by convincing experimental data that provide new insights into the interactions between melanoma cells and their environment.

Reviewed by eLife

An ERα-Dependent Hypoxia Response Defines EMT-Adjacent Tumour Regions and Suppresses the Pro-survival Effects of Amiloride in Estrogen Receptor-Positive Breast Cancer

1. Jodie R. Malcolm
2. Jack Stenning
3. Jacob Pope
4. Jakub Łukaszonek
5. Susanna F. Rose
6. Taylor E. Smith
7. Lesley Gilbert
8. Sally R. James
9. Katherine S. Bridge
10. William J. Brackenbury
11. Andrew N. Holding

Reviewed by Review Commons

Mutational and Expression Profile of ZNF217, ZNF750, ZNF703 Zinc Finger Genes in Kenyan Women Diagnosed with Breast Cancer

1. Michael Kitoi
2. John Gitau
3. Godfrey Wagutu
4. Kennedy Mwangi
5. Florence Ngonga
6. Francis Makokha

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding on the mutational landscape and expression profile of ZNF molecules in 23 Kenyan women with breast cancer. The evidence supporting the claims of the authors is solid, although inclusion of a larger number of patient samples, more statistical details and sufficient comparison with existing large-scale datasets would have strengthened the study. The work will be of interest to medical biologists working in the field of breast cancer.

Reviewed by eLife

High-Concordance Validation of Droplet Digital PCR and Next-Generation Sequencing for EGFR Mutation Detection Across Diverse Biospecimens in a Large-scale NSCLC Cohort Study

1. Ming Liu
2. Linping Lu
3. Lingxiang Zhu
4. Xiaoni Zhang
5. Yuanyuan Liu
6. Xiaojing Ren
7. Shimin Liu
8. Shaochen Cheng
9. Mingyan Xu
10. Chao Lu
11. Yan Peng
12. Wenmei Su
13. Yong Guo
14. Shifu Chen

Reviewed by PREreview

Candida albicans drives colorectal cancer progression by inducing hypoxia signaling

1. Wanqiu Wang
2. Mengqi Yang
3. Fanglei Gong
4. Zhenyu Zhang
5. Yanping Ma
6. Haihuang Li
7. Yu Zhao
8. Changzheng Du
9. Ningning Li
10. Guiwei He
11. Kun Sun

• Curated by eLife

  eLife Assessment

  This study examines the role of the fungal pathogen Candida albicans in the progression of colorectal cancer, a relevant and urgent topic given the global incidence of colon cancer. While the findings are useful and provide solid experimental work and insight into how Candida may contribute to tumor progression, the small patient sample size, reliance on in vitro models, and absence of in vivo validation may limit its impact. This work will interest scientists studying cancer progression and the role played by pathogens.

Reviewed by eLife

Predicting targeted- and immunotherapeutic response outcomes in melanoma with single-cell Raman spectroscopy and AI

1. Kai Chang
2. Mamatha Serasanambati
3. Baba Ogunlade
4. Hsiu-Ju Hsu
5. James Agolia
6. Ariel Stiber
7. Jeffrey Gu
8. Jay Chadokiya
9. Grayson E. Rodriguez
10. Prabhjeet Singh
11. Saurabh Sharma
12. Amanda Gonçalves
13. Ojasvi Verma
14. Fareeha Safir
15. Nhat Vu
16. K. Christopher Garcia
17. Daniel Delitto
18. Amanda Kirane
19. Jennifer A. Dionne

Reviewed by Arcadia Science

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