Cancer Biology

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

High-content microscopy reveals a morphological signature of bortezomib resistance

1. Megan E Kelley
2. Adi Y Berman
3. David R Stirling
4. Beth A Cimini
5. Yu Han
6. Shantanu Singh
7. Anne E Carpenter
8. Tarun M Kapoor
9. Gregory P Way

Reviewed by Review Commons

MYC disrupts transcriptional and metabolic circadian oscillations in cancer and promotes enhanced biosynthesis

1. Juliana Cazarin
2. Rachel E. DeRollo
3. Siti Noor Ain Binti Ahmad Shahidan
4. Jamison B. Burchett
5. Daniel Mwangi
6. Saikumari Krishnaiah
7. Annie L. Hsieh
8. Zandra E. Walton
9. Rebekah Brooks
10. Stephano S. Mello
11. Aalim M. Weljie
12. Chi V. Dang
13. Brian J. Altman

Reviewed by Review Commons

Lipid Droplets Fuel Small Extracellular Vesicle Biogenesis

1. Géraldine C. Genard
2. Luca Tirinato
3. Francesca Pagliari
4. Jessica Da Silva
5. Alessandro Giammona
6. Fatema Alquraish
7. Marie Bordas
8. Maria Grazia Marafioti
9. Simone Di Franco
10. Jeannette Janssen
11. Daniel Garcia-Calderón
12. Rachel Hanley
13. Clelia Nistico
14. Yoshinori Fukasawa
15. Torsten Müller
16. Jeroen Krijgsveld
17. Matilde Todaro
18. Francesco Saverio Costanzo
19. Giorgio Stassi
20. Michelle Nessling
21. Karsten Richter
22. Kendra K. Maass
23. Carlo Liberale
24. Joao Seco

Reviewed by Review Commons

Paralog dispensability shapes homozygous deletion patterns in tumor genomes

1. Barbara De Kegel
2. Colm J Ryan

Reviewed by Review Commons