Cancer Biology

Identification of a Musashi2 translocation as a novel oncogene in myeloid leukemia

1. Kyle Spinler
2. Michael Hamilton
3. Jeevisha Bajaj
4. Yutaka Shima
5. Emily Diaz
6. Marcie Kritzik
7. Tannishtha Reya

• Curated by eLife

  eLife assessment

  The study presents important findings on the role of MSI2-HOXA9 translocation in chronic myeloid leukemia. The authors provide convincing evidence supporting the role of this translocation in leukemogenesis by using elegant mouse modeling and in vitro mechanistic studies. Consistent with the reviews, the studies can be strengthened with further murine and cell line experiments.

Reviewed by eLife

RAPSYN-mediated neddylation of BCR-ABL alternatively determines the fate of Philadelphia chromosome-positive leukemia

1. Mengya Zhao
2. Beiying Dai
3. Xiaodong Li
4. Yixin Zhang
5. Chun Qiao
6. Yaru Qin
7. Zhao Li
8. Qingmei Li
9. Shuzhen Wang
10. Yong Yang
11. Yijun Chen

• Curated by eLife

  eLife assessment

  In this important study, the authors describe a novel function for RAPSYN in bcr-abl fusion associated leukemia, presenting convincing evidence that RAPSYN stabilizes the oncogenic BCR-ABL fusion protein. Compared to an earlier version of the manuscript, the authors have added data using primary samples that strengthen the conclusions.

Reviewed by eLife

Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability

1. Keene L Abbott
2. Ahmed Ali
3. Bradley I Reinfeld
4. Amy Deik
5. Sonu Subudhi
6. Madelyn D Landis
7. Rachel A Hongo
8. Kirsten L Young
9. Tenzin Kunchok
10. Christopher S Nabel
11. Kayla D Crowder
12. Johnathan R Kent
13. Maria Lucia L Madariaga
14. Rakesh K Jain
15. Kathryn E Beckermann
16. Caroline A Lewis
17. Clary B Clish
18. Alexander Muir
19. W Kimryn Rathmell
20. Jeffrey Rathmell
21. Matthew G Vander Heiden

• Curated by eLife

  eLife assessment

  This study provides an important finding that the local abundance of metabolites impacts the biology of the tumor microenvironment by utilizing kidney tumors from patients and adjacent normal tissues. The evidence supporting the claims of the authors is convincing. The work will of interest to the research community working on metabolism and kidney cancer especially.

Reviewed by eLife

mTORC1/S6K1 signaling promotes sustained oncogenic translation through modulating CRL3IBTK-mediated ubiquitination of eIF4A1 in cancer cells

1. Dongyue Jiao
2. Huiru Sun
3. Xiaying Zhao
4. Yingji Chen
5. Zeheng Lv
6. Qing Shi
7. Yao Li
8. Chenji Wang
9. Kun Gao

• Curated by eLife

  eLife assessment

  This study reports a novel substrate and a mediator of oncogenesis downstream of mTORC1, a fundamental advance in our understanding of the mechanistic basis of mTORC1-regulated cap-dependent translation and protein synthesis. Using an array of biochemical, proteomic and functional assays, the authors provide compelling evidence for a novel mTORC1/S6K1-IBTK-eIF4A1 signaling axis that promotes cancer pathogenic translation. This work is of broad interest and significance, given the importance of aberrant protein synthesis in cancer.

Reviewed by eLife

Internalisation of integrin-bound extracellular matrix modulates invasive carcinoma cell migration

1. Montserrat Llanses Martinez
2. Keqian Nan
3. Zhe Bao
4. Rachele Bacchetti
5. Shengnan Yuan
6. Joe Tyler
7. Xavier Le Guezennec
8. Frédéric A. Bard
9. Elena Rainero

Reviewed by Review Commons

Ribosome subunit attrition and activation of the p53–MDM4 axis dominate the response of MLL-rearranged cancer cells to WDR5 WIN site inhibition

1. Gregory Caleb Howard
2. Jing Wang
3. Kristie L Rose
4. Camden Jones
5. Purvi Patel
6. Tina Tsui
7. Andrea C Florian
8. Logan Vlach
9. Shelly L Lorey
10. Brian C Grieb
11. Brianna N Smith
12. Macey J Slota
13. Elizabeth M Reynolds
14. Soumita Goswami
15. Michael R Savona
16. Frank M Mason
17. Taekyu Lee
18. Stephen Fesik
19. Qi Liu
20. William P Tansey

• Curated by eLife

  eLife assessment

  This important paper reveals that one of the major roles of the WDR5 WIN site is to promote ribosome synthesis, and that by attacking the WIN site with inhibitors ribosome attrition occurs creating new vulnerabilities that can be therapeutically exploited. This deficiency of ribosomal proteins also provokes the p53 response. The data from a variety of approaches is generally very convincing, and together buttresses the authors' conclusions and interpretations quite nicely; overall, this paper will provide a justification for pre-clinical and translational studies of WDR5 interaction site inhibitors.

Reviewed by eLife

Multi-omic dataset of patient-derived tumor organoids of neuroendocrine neoplasms

1. Nicolas Alcala
2. Catherine Voegele
3. Lise Mangiante
4. Alexandra Sexton-Oates
5. Hans Clevers
6. Lynnette Fernandez-Cuesta
7. Talya L Dayton
8. Matthieu Foll

Reviewed by GigaScience

DUX4 is a common driver of immune evasion and immunotherapy failure in metastatic cancers

1. Jose Mario Bello Pineda
2. Robert K Bradley

• Curated by eLife

  eLife assessment

  This study presents a valuable finding on the association between DUX4 expression with features of immune evasion in human tissue and clinical outcomes in patients with advanced urothelial cancer. The evidence supporting the claims of the authors is convincing, using a range of corroborative statistical techniques. Compared to an earlier version, the quality of the manuscript has been enhanced, for example Figure 5 now illustrates the key features of survival probability estimates over time for patients assigned to with the test or training set.

Reviewed by eLife

mitoBKCa is functionally expressed in murine and human breast cancer cells and potentially contributes to metabolic reprogramming

1. Helmut Bischof
2. Selina Maier
3. Piotr Koprowski
4. Bogusz Kulawiak
5. Sandra Burgstaller
6. Joanna Jasińska
7. Kristian Serafimov
8. Monika Zochowska
9. Dominic Gross
10. Werner Schroth
11. Lucas Matt
12. David Arturo Juarez Lopez
13. Ying Zhang
14. Irina Bonzheim
15. Florian A Büttner
16. Falko Fend
17. Matthias Schwab
18. Andreas L Birkenfeld
19. Roland Malli
20. Michael Lämmerhofer
21. Piotr Bednarczyk
22. Adam Szewczyk
23. Robert Lukowski

• Curated by eLife

  eLife assessment

  The large-conductance Ca2+ activated K+ channel BKCa has been reported to promote breast cancer progression. The present study presents convincing evidence that an intracellular subpopulation of this channel reprograms breast cancer cells towards the Warburg phenotype, one of the metabolic hallmarks of cancer. This important finding advances the field of cancer cell metabolism and has potential therapeutic implications.

Reviewed by eLife

DHODH inhibition enhances the efficacy of immune checkpoint blockade by increasing cancer cell antigen presentation

1. Nicholas J Mullen
2. Surendra K Shukla
3. Ravi Thakur
4. Sai Sundeep Kollala
5. Dezhen Wang
6. Nina Chaika
7. Juan F Santana
8. William R Miklavcic
9. Drew A LaBreck
10. Jayapal Reddy Mallareddy
11. David H Price
12. Amarnath Natarajan
13. Kamiya Mehla
14. David B Sykes
15. Michael A Hollingsworth
16. Pankaj K Singh

• Curated by eLife

  eLife assessment

  This important study reports a novel mechanism linking DHODH inhibition and subsequent pyrimidine nucleotide depletion with upregulation of cell surface MHC I in cancer cells. The in vitro mechanistic data are compelling, with rigorous methodology and validation across multiple cell lines. The authors also provide in vivo evidence for additive effects of DHODH inhibitors and immune checkpoint blockade. However, the in vivo assessments of the functional relevance of this mechanism remain incomplete, requiring additional analyses to fully substantiate the conclusions made.

Reviewed by eLife