Cancer Biology

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

Oncogenic functions of the m6A demethylase FTO in breast cancer cells involving translational upregulation of C/EBPβ-LIP

1. Hidde R. Zuidhof
2. Christine Müller
3. Gertrud Kortman
4. René Wardenaar
5. Ekaterina Stepanova
6. Fabricio Loayza-Puch
7. Cornelis F. Calkhoven

Reviewed by Review Commons

The Drosophila cancer-germline, head-to-head gene pair TrxT and dhd is dispensable for normal brain development but plays a major role in l(3)malignant brain tumour growth

1. Cristina Molnar
2. Jan Peter Heinen
3. Jose Reina
4. Salud Llamazares
5. Emilio Palumbo
6. Giulia Pollarolo
7. Cayetano Gonzalez

Reviewed by Review Commons