Cancer Biology

Loss of ZNRF3/RNF43 Unleashes EGFR in Cancer

1. Fei Yue
2. Amy T. Ku
3. Payton D. Stevens
4. Megan N. Michalski
5. Weiyu Jiang
6. Jianghua Tu
7. Zhongcheng Shi
8. Yongchao Dou
9. Yi Wang
10. Xin-Hua Feng
11. Galen Hostetter
12. Xiangwei Wu
13. Shixia Huang
14. Noah F. Shroyer
15. Bing Zhang
16. Bart O. Williams
17. Qingyun Liu
18. Xia Lin
19. Yi Li

• Curated by eLife

  eLife assessment

  The main finding in this paper is that EGFR can be a novel substrate of the membrane ZNRF3/RNF43 E3 ligases. This is significant as the prevailing understanding posits that the Wnt receptors Frizzled and LRP5/6 exclusively served as substrates for these ligases. Given the frequent occurrence of mutations in ZNRF3/RNF43 or compromised expression levels in human cancers, the new evidence that aberrant EGFR expression and signaling may also contribute to the tumorigenic effects of ZNRF3/RNF43 mutations in cancer is important. The conclusions of the manuscript are supported by solid data, but some aspects of the mechanism presented need to be reinforced to fully support the claims made by the authors.

Reviewed by eLife

Exploiting a metabolic vulnerability in brain tumour stem cells using a brain-penetrant drug with safe profile

1. Audrey Burban
2. Cloe Tessier
3. Mathis Pinglaut
4. Joris Guyon
5. Johanna Galvis
6. Benjamin Dartigues
7. Maxime Toujas
8. Mathieu Larroquette
9. H Artee Luchman
10. Samuel Weiss
11. Nathalie Nicot
12. Barbara Klink
13. Macha Nikolski
14. Lucie Brisson
15. Thomas Mathivet
16. Andreas Bikfalvi
17. Thomas Daubon
18. Ahmad Sharanek

Reviewed by Review Commons

Convergent epigenetic evolution drives relapse in acute myeloid leukemia

1. Kevin Nuno
2. Armon Azizi
3. Thomas Koehnke
4. Caleb Lareau
5. Asiri Ediriwickrema
6. M Ryan Corces
7. Ansuman T Satpathy
8. Ravindra Majeti

• Curated by eLife

  eLife assessment

  This important work substantially advances our understanding of how resistant leukemia can arise without changes in mutational patterns by displaying epigenetic changes. The evidence supporting the conclusions is compelling, with rigorous genomic assays done on primary samples. and state-of-the-art microscopy. The work will be of broad interest to hematologists and cancer biologists.

Reviewed by eLife

Role of HAO2 in rats with chronic kidney disease by regulating fatty acid metabolic processes in renal tissue

1. Xunjia Li
2. Chengxuan Liu
3. Aimin Yang
4. Youfeng Shen
5. Jian Xu
6. Deyu Zuo

Reviewed by PREreview

Chromosomal instability induced in cancer can enhance macrophage-initiated immune responses that include anti-tumor IgG

1. Brandon H Hayes
2. Mai Wang
3. Hui Zhu
4. Steven H Phan
5. Lawrence J Dooling
6. Jason C Andrechak
7. Alexander H Chang
8. Michael P Tobin
9. Nicholas M Ontko
10. Tristan Marchena
11. Dennis E Discher

• Curated by eLife

  eLife assessment

  The authors provide compelling evidence that MSP1 inhibition (leading to chromosomal instability or CIN in the cancer cells) increases phagocytosis and that tumors with CIN respond better to macrophage therapeutics. In this important study, they demonstrate particularly impressive survival rates for mouse models of CIN B16 tumors treated with adoptively transferred macrophages, CD47-SIRPα blockade, and anti-Tyrp1 IgG.

Reviewed by eLife

Cannabinoid combination targets NOTCH1-mutated T-cell acute lymphoblastic leukemia through the integrated stress response pathway

1. Elazar Besser
2. Anat Gelfand
3. Shiri Procaccia
4. Paula Berman
5. David Meiri

• Curated by eLife

  eLife assessment

  This important study follows up on previous work defining the anti-leukemic effects of a previously characterized cannabis extract on Notch-activated T cells and identifies several pathways that mediate its anti-cancer activity including the ER calcium and integrated stress response. The evidence is solid, but several concerns remain including the over reliance on a single cell line for the majority of the studies and lack of integration of the observations with existing literature

Reviewed by eLife

Telomere length sensitive regulation of Interleukin Receptor 1 type 1 (IL1R1) by the shelterin protein TRF2 modulates immune signalling in the tumour microenvironment

1. Ananda Kishore Mukherjee
2. Subhajit Dutta
3. Ankita Singh
4. Shalu Sharma
5. Shuvra Shekhar Roy
6. Antara Sengupta
7. Megha Chatterjee
8. Soujanya Vinayagamurthy
9. Sulochana Bagri
10. Divya Khanna
11. Meenakshi Verma
12. Dristhi Soni
13. Anshul Budharaja
14. Sagar Kailasrao Bhisade
15. Vivekanand
16. Ahmad Perwez
17. Nija George
18. Mohammed Faruq
19. Ishaan Gupta
20. Radhakrishnan Sabarinathan
21. Shantanu Chowdhury

• Curated by eLife

  eLife assessment

  This study presents an important finding on the role of telomeres in modulating interleukin-1 signaling and tumor immunity in TNBC. The evidence supporting these findings is solid, presented through comprehensive analyses including TNBC clinical samples, tumor-derived organoids, cancer cells, and xenografts. The work will be of broad interest to cell and medical biologists focusing on TNBC.

Reviewed by eLife

Exploration of drug resistance mechanisms in triple negative breast cancer cells using a microfluidic device and patient tissues

1. Wanyoung Lim
2. Inwoo Hwang
3. Jiande Zhang
4. Zhenzhong Chen
5. Jeonghun Han
6. Jaehyung Jeon
7. Bon-Kyoung Koo
8. Sangmin Kim
9. Jeong Eon Lee
10. Youngkwan Kim
11. Kenneth J Pienta
12. Sarah R Amend
13. Robert H Austin
14. Jee-Yin Ahn
15. Sungsu Park

• Curated by eLife

  eLife assessment

  This study based on the use of Cancer Drug Resistance Accelerator (CDRA) chip is valuable as a platform technology to assess chemoresistance mechanisms. The strength is convincing from the technological point of view. However, the use of a single cell line model is a limitation. However we acknowledge the authors' plan to further validate their current findings across multiple TNBC cell lines.

Reviewed by eLife

Mechanically stimulated osteocytes maintain tumor dormancy in bone metastasis of non-small cell lung cancer by releasing small extracellular vesicles

1. Jing Xie
2. Yafei Xu
3. Xuhua Liu
4. Li Long
5. Ji Chen
6. Chunyan Huang
7. Yan Shao
8. Zhiqing Cai
9. Zhimin Zhang
10. Ruixin Zhou
11. Jiarong Leng
12. Xiaochun Bai
13. Qiancheng Song

• Curated by eLife

  eLife assessment

  This is an important study, that adds to the field a new understanding of exercise or mechanical loading, microRNAs, and secreted extracellular vessicles in the field of lung cancer (NSCLC), which may have relevance to other osteolytic cancers. The strength of the evidence was mixed: whereas in vitro microRNA experiments were convincing, other elements were incomplete (e.g., proving the roles of osteocytes, as opposed to other mechanosensitive cells, in vivo). This work would be of broad interest to those investigating osteolytic cancers, and the role of exercise in bone cancer, preclinically.

Reviewed by eLife

Combinatorial CRISPR screen reveals FYN and KDM4 as targets for synergistic drug combination for treating triple negative breast cancer

1. Tackhoon Kim
2. Byung-Sun Park
3. Soobeen Heo
4. Heeju Jeon
5. Jaeyeal Kim
6. Donghwa Kim
7. Sang Kook Lee
8. So-Youn Jung
9. Sun-Young Kong
10. Timothy K. Lu

• Curated by eLife

  eLife assessment

  This study presents a valuable finding on the roles and mechanisms of FYN and KDM4 in TNBC tumor cell resistance. The evidence supporting the claims of the authors is somewhat incomplete and the refinement of certain experiments would have strengthened the study. Noteworthy, FYN has been implied in drug resistance previously and this should be carefully discussed in the manuscript. The work will be of interest to scientists working on breast cancer.

Reviewed by eLife