Cancer Biology

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

Single-cell multiomics analysis of chronic myeloid leukemia links cellular heterogeneity to therapy response

1. Rebecca Warfvinge
2. Linda Geironson Ulfsson
3. Parashar Dhapola
4. Fatemeh Safi
5. Mikael Sommarin
6. Shamit Soneji
7. Henrik Hjorth-Hansen
8. Satu Mustjoki
9. Johan Richter
10. Ram Krishna Thakur
11. Göran Karlsson

• Curated by eLife

  eLife assessment

  This study presents fundamental insights into the heterogeneity of chronic myeloid leukemia (CML) stem cells and their response to tyrosine kinase inhibitor therapy, shedding light on potential mechanisms underlying treatment failure. The study's robust methodology, supported by validation with bulk RNA-seq data and surface marker analysis, provides compelling evidence for the identified associations between cellular composition and treatment outcome. These findings contribute to our understanding of CML pathogenesis and may inform the development of more targeted therapeutic strategies.

Reviewed by eLife

SOD1 is a synthetic-lethal target in PPM1D-mutant leukemia cells

1. Linda Zhang
2. Joanne I Hsu
3. Etienne D Braekeleer
4. Chun-Wei Chen
5. Tajhal D Patel
6. Alejandra G Martell
7. Anna G Guzman
8. Katharina Wohlan
9. Sarah M Waldvogel
10. Hidetaka Uryu
11. Ayala Tovy
12. Elsa Callen
13. Rebecca L Murdaugh
14. Rosemary Richard
15. Sandra Jansen
16. Lisenka Vissers
17. Bert BA de Vries
18. Andre Nussenzweig
19. Shixia Huang
20. Cristian Coarfa
21. Jamie Anastas
22. Koichi Takahashi
23. George Vassiliou
24. Margaret A Goodell

• Curated by eLife

  eLife assessment

  Gain-of-function mutations and amplifications of PPM1D are found across several human cancers and are associated with advanced tumor stage and worse prognosis. Thus far, the clinical translation has not been possible due to the lack of PPM1D inhibitors with favorable pharmacokinetic properties. This useful study leverages CRISPR/Cas9 screening to determine that loss of SOD1 and is synthetic lethal with PPM1D mutation in leukemia. The mechanistic analyses are still incomplete.

Reviewed by eLife

CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake

1. Savvas Nikolaou
2. Amelie Juin
3. Jamie A Whitelaw
4. Nikki R Paul
5. Loic Fort
6. Colin Nixon
7. Heather J Spence
8. Sheila Bryson
9. Laura M Machesky

• Curated by eLife

  eLife assessment

  This important study combines in vivo and in vitro models to characterise the role of CYRI-B, an interactor of the small GTPase Rac1, in controlling pancreatic cancer progression towards a higher proliferative and metastatic stage. The evidence supporting the claims of the authors is convincing in characterizing a novel Rac1 binding protein, CYRI-B, as a regulator of metastatic potential in vivo, with distinct functions at different stages of tumour progression. CYRI-B reduces the typical hyperactivation of Rac1 in the early stages of tumour progression; subsequently, CYRI-B mediates internalization of lysophosphatidic acid receptor 1 (LPAR1) uptake through macropinocytosis, thus regulating chemotactic migration of cancer cells towards lysophosphatidic acid (LPA). Although the inclusion of human pancreatic cancer cell lines would have strengthened the study, the work will be of broad interest to cell biologists and the signalling research communities.

Reviewed by eLife

DePARylation is critical for S phase progression and cell survival

1. Litong Nie
2. Chao Wang
3. Min Huang
4. Xiaoguang Liu
5. Xu Feng
6. Mengfan Tang
7. Siting Li
8. Qinglei Hang
9. Hongqi Teng
10. Xi Shen
11. Li Ma
12. Boyi Gan
13. Junjie Chen

• Curated by eLife

  eLife assessment

  The demonstration that the PARG dePARylation enzyme is required in S phase to remove polyADP-ribose (PAR) protein adducts that are generated in response to the presence of unligated Okazaki fragments is potentially valuable, but the evidence is incomplete, and identification of relevant PARylated PARG substrates in S-phase is needed to understand the role of PARP1-mediated PARylation and PARG-catalyzed dePARylation in S-phase progression.

Reviewed by eLife

Loss of tumor suppressor TMEM127 drives RET-mediated transformation through disrupted membrane dynamics

1. Timothy J Walker
2. Eduardo Reyes-Alvarez
3. Brandy D Hyndman
4. Michael G Sugiyama
5. Larissa CB Oliveira
6. Aisha N Rekab
7. Mathieu JF Crupi
8. Rebecca Cabral-Dias
9. Qianjin Guo
10. Patricia LM Dahia
11. Douglas S Richardson
12. Costin N Antonescu
13. Lois M Mulligan

• Curated by eLife

  eLife assessment

  This valuable paper provides convincing evidence that loss of the tumor suppressor TMEM127 causes disorganization of plasma membrane lipid domains, alters clathrin assembly, and inhibits endocytosis of a variety of cell surface receptors, leading to increased cell surface levels of signaling proteins including RET and other transmembrane receptor tyrosine kinases. The results are significant for understanding how RET127 loss contributes to pheochromocytoma, although the evidence is indirect owing to the lack of human pheochromocytoma cell lines. The results will be of interest for researchers studying pheochromocytoma and endocytosis mechanisms.

Reviewed by eLife

STAT3 is a genetic modifier of TGF-beta induced EMT in KRAS mutant pancreatic cancer

1. Stephen D'Amico
2. Varvara Kirillov
3. Oleksi Petrenko
4. Nancy C Reich

• Curated by eLife

  eLife assessment

  This study delves into the complex role of STAT3 signaling and its interplay with TGF-beta and SMAD4 in KRAS mutant pancreatic cancer. The authors demonstrate that both the presence and absence of STAT3, relative to SMAD4, can lead to poor PDAC differentiation and that STAT3 mutations affect p53-null fibroblasts with KRASG12D and induce an EMT-like phenotype. By providing convincing evidence, the authors were able to derive important insights into KRAS mutant cancers.

Reviewed by eLife