Cancer Biology

Myosin VI orchestrates estrogen-driven gene expression in breast cancer cells

1. Yukti Hari-Gupta
2. Danielle Lambert
3. Isabel W. Shahid-Fuente
4. Natalia Fili
5. Ália dos Santos
6. Alexandria Sprules
7. Hyejeong Rosemary Kim
8. Alexander W. Cook
9. Peter J.I. Ellis
10. Jesse Aaron
11. Teng-Leong Chew
12. Lin Wang
13. Christopher P. Toseland

Reviewed by PREreview

Identifying tissue states by spatial protein patterns related to chemotherapy response in triple-negative breast cancer

1. Luciana M Luque
2. Mohammad Asif Khan
3. Giuseppe Torrisi
4. Tessa D Green
5. David Hardman
6. Claudia Owczarek
7. Tom A Phillips
8. Debora S Marks
9. Maddy Parsons
10. Chris Sander
11. Linus J Schumacher

• Curated by eLife

  eLife Assessment

  This is an important work implementing data mining methods on IMC data to discover spatial protein patterns related to the triple-negative breast cancer patients' chemotherapy response. The evidence supporting the claims of the authors is solid, although more detailed methodology clarification and validation are needed. While the accuracy of the methods is not very high, the work shows potential for translational application.

Reviewed by eLife

Molecular and Functional Analysis of Calcium Binding by a Cancer-linked Calreticulin Mutant

1. Ishmael Nii Ayibontey Tagoe
2. Amanpreet Kaur
3. Osbourne Quaye
4. Emmanuel Ayitey Tagoe
5. Nicole Koropatkin
6. Leslie S Satin
7. Malini Raghavan

• Curated by eLife

  eLife Assessment

  This study investigates low-affinity Ca2+ binding by WT calreticulin and mutant calreticulin associated with type I myeloproliferative neoplasms, as well as the impact on Ca2+ fluxes in suspension cultures of megakaryocyte-like cells in vitro in response to ER Ca2+ ATPase inhibitors that deplete endoplasmic reticulum (ER) Ca2+ store and open plasma membrane Ca2+ channels through STIM1-Orai interactions. The results are important in that they show that Ca2+ binding by calreticulin and store-operated Ca2+ entry are not fundamentally impacted by the type I deletion mutation in calreticulin, which rules out a direct effect of the calreticulin mutation on its own low-affinity Ca2+ binding and any broad impact on ER Ca2+ regulation. The strength of the data and methods used ranges from solid to convincing, although the use of suspension-based flow cytometric assays to investigate ER Ca2+ levels and Ca2+ entry can be challenged. High-affinity Ca2+ binding sites could be further considered, and possible confounding effects of Abl kinase activity in the megakaryocyte-like cell lines could be offset.

Reviewed by eLife

p53-induced RNA-binding protein ZMAT3 inhibits transcription of a hexokinase to suppress mitochondrial respiration in human cancer cells

1. Ravi Kumar
2. Simon Couly
3. Bruna R Muys
4. Xiao Ling Li
5. Ioannis Grammatikakis
6. Ragini Singh
7. Mary Guest
8. Xinyu Wen
9. Wei Tang
10. Stefan Ambs
11. Lisa M Jenkins
12. Erica C Pehrsson
13. Raj Chari
14. Tsung-Ping Su
15. Ashish Lal

• Curated by eLife

  eLife Assessment

  In this study, the authors investigate the role of ZMAT3, a p53 target gene, in tumor suppression and RNA splicing regulation. Using quantitative proteomics, the authors uncover that ZMAT3 knockout leads to upregulation of HKDC1, a gene linked to mitochondrial respiration, and that ZMAT3 suppresses HKDC1 expression by inhibiting c-JUN-mediated transcription. This set of convincing evidence reveals a fundamental mechanism by which ZMAT3 contributes to p53-driven tumor suppression by regulating mitochondrial respiration.

Reviewed by eLife

Mitochondrial protein carboxyl-terminal alanine-threonine tailing promotes human glioblastoma growth by regulating mitochondrial function

1. Bei Zhang
2. Ting Cai
3. Esha Reddy
4. Yuanna Wu
5. Isha Mondal
6. Yinglu Tang
7. Adaeze Scholastical Gbufor
8. Jerry Wang
9. Yawei Shen
10. Qing Liu
11. Raymond Sun
12. Winson S Ho
13. Rongze Olivia Lu
14. Zhihao Wu

• Curated by eLife

  eLife Assessment

  Glioblastoma is among the most aggressive cancers without a cure, and its cells are characterized by high mitochondrial membrane potential. This manuscript provides convincing evidence that glioblastoma tumorigenesis is closely linked to mitochondrial stress. The study makes a valuable contribution to the field by advancing our understanding of the metabolic mechanisms driving glioblastoma and highlighting potential therapeutic targets.

Reviewed by eLife

Punctuated mutagenesis promotes multi-step evolutionary adaptation in human cancers

1. Christopher Graser
2. Wenbo Wu
3. Cole Christini
4. Mia Petljak
5. Franziska Michor

• Curated by eLife

  eLife Assessment

  This valuable study presents a theoretical model of how punctuated mutations influence multistep adaptation, supported by empirical evidence from some TCGA cancer cohorts. This solid model points to the case of possible punctuated evolution rather than gradual genomic change. There was some disagreement amongst the reviewers in terms of how closely the theoretical results apply to the phenomena examined empirically, and alternative explanations should be considered in the future.

Reviewed by eLife

CNN-based learning of single-cell transcriptomes reveals a blood-detectable multi-cancer signature of brain metastasis

1. Ryan Lusby
2. Debojyoti Chowdhury
3. Sarah Carl
4. Vijay K Tiwari

• Curated by eLife

  eLife Assessment

  This important study describes a deep learning framework that analyzes single-cell RNA data to identify a tumor-agnostic gene signature associated with brain metastases. The identified signature uncovers key molecular mechanisms, highlights potential therapeutic targets, and demonstrates a metastasis-specific transcriptional signal in circulating platelets, suggesting its promise for non-invasive diagnostics through liquid biopsy. The evidence supporting the findings is solid, utilizing interpretable deep learning methodologies and large-scale datasets across multiple cancer types, though some aspects may benefit from additional analysis and validation.

Reviewed by eLife

Androgen deprivation triggers a cytokine signaling switch to induce immune suppression and prostate cancer recurrence

1. Kai Sha
2. Renyuan Zhang
3. Aerken Maolake
4. Shalini Singh
5. Gurkamal Chatta
6. Kevin H Eng
7. Kent L Nastiuk
8. John J Krolewski

• Curated by eLife

  eLife Assessment

  This potentially valuable work aimed at a better understanding of the mechanisms of response and resistance to androgen deprivation therapy in prostate cancer using genetically engineered mouse models. A key observation relates to the timing of TNF blockage therapy and the concept of a "TNF switch." The solid data were collected using conventional approaches and the conclusions are mostly justified, particularly with the inclusion of more detailed statistics in the revision. The work will be of interest to the prostate cancer research community.

Reviewed by eLife

Transcriptional subtypes on immune microenvironment and predicting postoperative recurrence and metastasis in human pheochromocytoma and paraganglioma

1. Yang Liu
2. Xu Yan
3. Yibo Zhang
4. Zhenfu Gao
5. Fengrui Nan
6. Siyu Shi
7. Jingyun Chen
8. Lingyu Li

• Curated by eLife

  eLife Assessment

  This is a valuable study describing transcriptome-based pheochromocytoma and paraganglioma (PPGL) subtypes and exploring the mutations, immune correlates and disease progression of cases in each subtype. The cohort is a reasonable size and a second cohort is included from the Cancer Genome Atlas (TCGA). One of the key premises of the study is that identification of driver mutations in PPGL is not complete and that compromises characterisation for prognostic purposes. This is a solid starting point on which to base characterisation using different methods.

Reviewed by eLife

Pharmacologic inhibition of BAF chromatin remodeling complexes as a therapeutic approach to transcription factor-dependent cancers

1. Richard C Centore
2. Luis MM Soares
3. Salih Topal
4. Rishi G Vaswani
5. Kana Ichikawa
6. Zhifang Li
7. Hong Fan
8. Jeremy W Setser
9. David L Lahr
10. Laura E Zawadzke
11. Xueying Chen
12. Kimberly D Barnash
13. Jordana Muwanguzi
14. Neville Anthony
15. Gabriel J Sandoval
16. Katharine Feldman
17. GiNell Elliott
18. Ammar Adam
19. David Huang
20. Yunji Davenport
21. Shawn Schiller
22. Kevin J Wilson
23. Johannes Voigt
24. Lan Xu
25. Martin Hentemann
26. David S Millan
27. Ho Man Chan
28. Carl P Decicco
29. Ryan G Kruger
30. Gromoslaw A Smolen
31. Steven F Bellon

• Curated by eLife

  eLife Assessment

  This study constitutes a fundamental advance for the uveal melanoma research field that might be exploited to target this deadly cancer and more generally for targeting transcriptional dependency in cancers. This work substantially advances our understanding of pharmacological inhibition of SWI/SNF as a therapeutic approach for cancer. The study is well written and provides compelling evidence, including comprehensive datasets, compound screens, gene expression analysis, epigenetics, as well as animal studies.

Reviewed by eLife