Cancer Biology

Mitochondrial stress-induced protein carboxyl-terminal alanine threonine tailing (msiCAT-tailing) facilitates glioblastoma tumorigenesis through the modulation of mitochondrial functions

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

Repression of PRMT activities sensitize homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatment

1. Youyou Zhang
2. Mu Xu
3. Jiao Yuan
4. Zhongyi Hu
5. Junjie Jiang
6. Yanrong Sun
7. Jie Huang
8. Yuxin Wang
9. Bingwei Wang
10. Jianfeng Shen
11. Meixiao Long
12. Yi Fan
13. Kathleen T Montone
14. Janos L Tanyi
15. Sarah H Kim
16. Omid Tavana
17. Robert H Vonderheide
18. Ho Man Chan
19. Susan M Domchek
20. Lin Zhang
21. Xiaowen Hu

• Curated by eLife

  eLife Assessment

  This study presents a valuable and interesting finding that a combination of arginine methyltransferase inhibitors synergize with PARP inhibitors to eliminate ovarian and triple negative cancer cell lines in vitro and in vivo using preclinical mouse models. The data were collected and analyzed using solid and validated methodology and can be used as a starting point for the development of novel therapeutics. The work will be of broad interest to scientists working in the field of breast cancer and ovarian cancer.

Reviewed by eLife

Spatially defined multicellular functional units in colorectal cancer revealed from single cell and spatial transcriptomics

1. Inbal Avraham-Davidi
2. Simon Mages
3. Johanna Klughammer
4. Noa Moriel
5. Shinya Imada
6. Matan Hofree
7. Evan Murray
8. Jonathan Chen
9. Karin Pelka
10. Arnav Mehta
11. Genevieve M Boland
12. Toni Delorey
13. Leah Caplan
14. Danielle Dionne
15. Robert Strasser
16. Jana Lalakova
17. Anezka Niesnerova
18. Hao Xu
19. Morgane Rouault
20. Itay Tirosh
21. Nir Hacohen
22. Fei Chen
23. Omer Yilmaz
24. Jatin Roper
25. Orit Rozenblatt-Rosen
26. Mor Nitzan
27. Aviv Regev

• Curated by eLife

  eLife Assessment

  This work presents a valuable resource combining scRNA-seq and spatial transcriptomics studies to map mouse pre-clinical models of colorectal cancer, identifying distinct cellular programs and microenvironments that could enhance patient stratification and therapeutic approaches in colorectal cancer. While the evidence provided in the manuscript are not fully validated, these solid data were collected and analyzed using a validated methodology that will be of interest to the community in future studies.

Reviewed by eLife

TopBP1 biomolecular condensates as a new therapeutic target in advanced-stage colorectal cancer

1. Laura Morano
2. Nadia Vezzio-Vié
3. Adam Aissanou
4. Tom Egger
5. Antoine Aze
6. Solène Fiachetti
7. Benoit Bordignon
8. Cedric Hassen-khodja
9. Hervé Seitz
10. Louis-Antoine Milazzo
11. Véronique Garambois
12. Laurent Chaloin
13. Nathalie Bonnefoy
14. Céline Gongora
15. Angelos Constantinou
16. Jihane Basbous

• Curated by eLife

  eLife Assessment

  This valuable study reveals that the GSK-3 inhibitor AZD2858 inhibits the formation of TOPBP1 condensates and hence DNA damage responses in colorectal cancer cells. The evidence supporting the claims of the authors is convincing, although uncovering how this drug blocks bio-condensate formation would have strengthened the study. The work will be of interest to cancer researchers searching for synergistic drug combination strategies.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife

Rearrangement of 3D genome organization in breast cancer epithelial to mesenchymal transition and metastasis organotropism

1. Priyojit Das
2. Rebeca San Martin
3. Tian Hong
4. Rachel Patton McCord

• Curated by eLife

  eLife Assessment

  This valuable study explores the role of spatial genome organization in oncogenic transformation, addressing an ambitious and significant topic. The authors have assembled comprehensive datasets from various subtypes of localized and lung-metastatic breast cancer cells, as well as from healthy and cancerous lung cells. They identified switching patterns in the 3D genome organization of lung-metastatic breast cancer cells, revealing a reconfiguration of genome architecture that resembles that of lung cells. This provides solid evidence with significant biomedical implications for epigenetic regulation in both normal physiology and disease.

Reviewed by eLife

Molecular consequences of acute versus chronic CDK12 loss in prostate carcinoma nominates distinct therapeutic strategies

1. Sander Frank
2. Thomas Persse
3. Ilsa Coleman
4. Armand Bankhead
5. Dapei Li
6. Navonil De-Sarkar
7. Divin Wilson
8. Dmytro Rudoy
9. Manasvita Vashisth
10. Patty Galipeau
11. Michael Yang
12. Brian Hanratty
13. Ruth Dumpit
14. Colm Morrissey
15. Eva Corey
16. R Bruce Montgomery
17. Michael C Haffner
18. Colin C Pritchard
19. Valeri Vasioukhin
20. Gavin Ha
21. Peter S Nelson

• Curated by eLife

  eLife Assessment

  The paper is a fundamental study examining the role of CDK12 loss in prostate cancer. While previous studies have suggested that CDK12 loss confers HRD phenotypes, clinical trials using PARPi in CDK12 altered patients have not demonstrated significant benefit. This work investigates these mechanisms in depth and provides compelling evidence. A comprehensive genomic analysis serves an excellent resource to the field, showing that biallelic CDK12 alterations do not have genomic features of HRd. Moreover, the study explored both acute and chronic deletion of CDK12, with data suggestive of CDK12-altered cells being uniquely sensitive to CDK13 inhibition. While some minor weaknesses have been previously noted by the reviewers, the authors have adequately addressed these concerns with appropriate rigor.

Reviewed by eLife

BEHAV3D Tumor Profiler to map heterogeneous cancer cell behavior in the tumor microenvironment

1. Emilio Rios-Jimenez
2. Anoek Zomer
3. Raphael Collot
4. Mario Barrera Román
5. Sandra F Archidona
6. Hendrikus Ariese
7. Ravian van Ineveld
8. Michiel Kleinnijenhuis
9. Nils Bessler
10. Hannah Johnson
11. Caleb A Dawson
12. Anne Rios
13. Maria Alieva

• Curated by eLife

  eLife Assessment

  This is a useful tool for code-less analysis of patterns in cell migratory behaviours in vivo using intravital microscopy data and allows correlation with spatial features of the tumour microenvironment. There is a clear need for these tools to make quantitative analysis, comparison and interpretation of complex cell tracking data more accessible and solid evidence is provided of its applicability to tracks generated by both proprietary and open tracking software.

Reviewed by eLife

Proteomic profiling of advanced hepatocellular carcinoma identifies predictive signatures of response to treatments

1. Adèle Delamarre
2. Marie Decraecker
3. Jean-Frédéric Blanc
4. Sylvaine Di Tommaso
5. Cyril Dourthe
6. Jean-William Dupuy
7. Mélanie Moreau
8. Nathalie Allain
9. Isabelle Mahouche
10. Julie Giraud
11. Giovanni Bénard
12. Claude Lalou
13. Benoît Pinson
14. Paulette Bioulac-Sage
15. Caroline Toulouse
16. Audrey Morisset
17. Jérôme Boursier
18. Brigitte Le Bail
19. Anne-Aurélie Raymond
20. Frédéric Saltel

Reviewed by PREreview

KDM5 demethylases suppress R-loop-mediated ‘viral mimicry’ and DNA damage in breast cancer cells

1. Lena Lau
2. Kurt Henderson
3. Ahu Turkoz
4. Sara Linker
5. Dorte Schlessinger
6. Brad Townsley
7. Brian Egan
8. Shoba Ragunathan
9. Robert Rollins
10. Xianju Bi
11. Zhijian J Chen
12. Oleg Brodsky
13. Clifford Restaino
14. Murali Gururajan
15. Kristen Jensen-Pergakes
16. Anders Mälarstig
17. Chames Kermi
18. Paul Moore
19. Marie Classon

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding that KDM5 inhibitors may enable a wide therapeutic window as compared to STING agonists or Type I Interferons. The evidence supporting the claims of the authors is convincing. The work will be of broad interest to scientists working in the field of breast cancer research.

Reviewed by eLife

Developmental programmes drive cellular plasticity, disease progression and therapy resistance in lung adenocarcinoma

1. Kamila J Bienkowska
2. Stephany Gallardo Y
3. Nur S Zainal
4. Matthew Ellis
5. Maria-Antoinette Lopez
6. Judith Austine
7. Sai Pittla
8. Serena J Chee
9. Aiman Alzetani
10. Emily C Shaw
11. Christian H Ottensmeier
12. Gareth J Thomas
13. Christopher J Hanley

Reviewed by Review Commons