Cancer Biology

Low HER2 expression in normal breast epithelium enables dedifferentiation and malignant transformation via chromatin opening

1. Ateequllah Hayat
2. Edward P. Carter
3. Hamish W. King
4. Aysegul Ors
5. Aaron Doe
6. Saul A. Teijeiro
7. Sarah Charrot
8. Susana Godinho
9. Pedro Cutillas
10. Hisham Mohammed
11. Richard P. Grose
12. Gabriella Ficz

Reviewed by Review Commons

EHD2 overexpression promotes tumorigenesis and metastasis in triple-negative breast cancer by regulating store-operated calcium entry

1. Haitao Luan
2. Timothy A Bielecki
3. Bhopal C Mohapatra
4. Namista Islam
5. Insha Mushtaq
6. Aaqib M Bhat
7. Sameer Mirza
8. Sukanya Chakraborty
9. Mohsin Raza
10. Matthew D Storck
11. Michael S Toss
12. Jane L Meza
13. Wallace B Thoreson
14. Donald W Coulter
15. Emad A Rakha
16. Vimla Band
17. Hamid Band

• Curated by eLife

  eLife assessment

  This study, supported by reasonably solid evidence, will be of interest to breast cancer researchers. The finding that EHD2 promotes tumor growth and impacts store-operated calcium entry (SOCE) adds to our understanding of breast cancer cell physiology. If supported by further research, the study provides a rationale for using SOCE inhibitors in a subset of breast cancers, with high expression of EHD2 serving as a potential predictive biomarker for using SOCE inhibitors.

Reviewed by eLife

EZH2/hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression

1. Zong-Shin Lin
2. Chiao-Chen Chung
3. Yu-Chia Liu
4. Chu-Han Chang
5. Hui-Chia Liu
6. Yung-Yi Liang
7. Teng-Le Huang
8. Tsung-Ming Chen
9. Che-Hsin Lee
10. Chih-Hsin Tang
11. Mien-Chie Hung
12. Ya-Huey Chen

• Curated by eLife

  eLife assessment

  In this study, Hung et al. address the biology and therapy of chondrosarcoma. The authors provided high-quality data that uncovered a new signaling axis, EZH2/hSULF1/c-Met, that promotes chondrosarcoma growth and progress. The authors also reported evidence showing that c-Met inhibition may be a plausible treatment option for chondrosarcoma. The findings are novel and translational and are of interest to cancer biologists and oncologists.

Reviewed by eLife

Weakly migratory metastatic breast cancer cells activate fibroblasts via microvesicle-Tg2 to facilitate dissemination and metastasis

1. Samantha C Schwager
2. Katherine M Young
3. Lauren A Hapach
4. Caroline M Carlson
5. Jenna A Mosier
6. Tanner J McArdle
7. Wenjun Wang
8. Curtis Schunk
9. Anissa L Jayathilake
10. Madison E Bates
11. Francois Bordeleau
12. Marc A Antonyak
13. Richard A Cerione
14. Cynthia A Reinhart-King

• Curated by eLife

  eLife assessment

  The interesting manuscript shows that breast cancer cells that are poorly migratory in culture can be more metastatic in mice. This is due, at least in part, to the secretion of extracellular vesicles containing the the crosslinking enzyme Transglutaminase-2, which can activate fibroblasts in the tumours. These fibroblasts can then promote metastatic phenotypes. This study demonstrates how cancer cells can manipulate the cells around them in order to disseminate.

Reviewed by eLife

Collateral deletion of the mitochondrial AAA+ ATPase ATAD1 sensitizes cancer cells to proteasome dysfunction

1. Jacob M Winter
2. Heidi L Fresenius
3. Corey N Cunningham
4. Peng Wei
5. Heather R Keys
6. Jordan Berg
7. Alex Bott
8. Tarun Yadav
9. Jeremy Ryan
10. Deepika Sirohi
11. Sheryl R Tripp
12. Paige Barta
13. Neeraj Agarwal
14. Anthony Letai
15. David M Sabatini
16. Matthew L Wohlever
17. Jared Rutter

• Curated by eLife

  eLife assessment

  The authors identify co-deletion of the mitochondrial AAA+ ATPase ATAD1 with the tumor suppressor PTEN as a factor modifying cancer prognosis, based on a new mechanism of increasing sensitivity to proteotoxic stress induced by proteasome inhibition. The authors also identify the mitochondrial E3 ubiquitin ligase MARCH5 as a gene whose deletion is synthetically lethal with ATAD1. These findings suggest that the use of proteasome-targeting agents may be useful in patients with tumors dually deleted for ATAD1 and PTEN. The study is based on convincing evidence, and makes an innovative contribution to the understanding of the biology of tumors with 10q23 deletions.

Reviewed by eLife

Targeting the fatty acid binding proteins disrupts multiple myeloma cell cycle progression and MYC signaling

1. Mariah Farrell
2. Heather Fairfield
3. Michelle Karam
4. Anastasia D'Amico
5. Connor S Murphy
6. Carolyne Falank
7. Romanos Sklavenitis Pistofidi
8. Amanda Cao
9. Catherine R Marinac
10. Julie A Dragon
11. Lauren McGuinness
12. Carlos G Gartner
13. Reagan Di Iorio
14. Edward Jachimowicz
15. Victoria DeMambro
16. Calvin Vary
17. Michaela R Reagan

• Curated by eLife

  eLife assessment

  This manuscript will be of interest to researchers within the fields of haematological and bone oncology. It reveals a novel effect of FABP5 inhibition to reduce myeloma growth both in vitro and in vivo, with convincing supporting associations between FABP5 expression and survival in patients with myeloma.

Reviewed by eLife

Alternative splicing downstream of EMT enhances phenotypic plasticity and malignant behavior in colon cancer

1. Tong Xu
2. Mathijs Verhagen
3. Rosalie Joosten
4. Wenjie Sun
5. Andrea Sacchetti
6. Leonel Munoz Sagredo
7. Véronique Orian-Rousseau
8. Riccardo Fodde

• Curated by eLife

  eLife assessment

  This study provides a valuable analysis of the splicing landscape in colon cancer cells that have properties intermediate between those typically found in primary cancers ("epithelial") and those that are spreading by metastasis ("mesenchymal"). The strength of evidence provided is wide ranging and convincing, and supports current ideas that changes in the way that RNA from particular genes is processed plays a key role in cancer spread.

Reviewed by eLife

VPS9D1-AS1 overexpression amplifies intratumoral TGF-β signaling and promotes tumor cell escape from CD8+ T cell killing in colorectal cancer

1. Lei Yang
2. Xichen Dong
3. Zheng Liu
4. Jinjing Tan
5. Xiaoxi Huang
6. Tao Wen
7. Hao Qu
8. Zhenjun Wang

• Curated by eLife

  eLife assessment

  This research focuses on the role of a long noncoding RNA VPS9D1-AS1(VPS) in colorectal cancer (CRC) immune evasion and provides evidence on how it is responsible for escape from cytotoxic T cells killing via amplifying intra-tumoral TGF-β signaling. The findings are of considerable translational significance since VPS9D1-AS1 was validated targetable in this work, and it is of broad interest to readers in cancer biology and immunotherapy.

Reviewed by eLife

Defining function of wild-type and three patient-specific TP53 mutations in a zebrafish model of embryonal rhabdomyosarcoma

1. Jiangfei Chen
2. Kunal Baxi
3. Amanda E Lipsitt
4. Nicole Rae Hensch
5. Long Wang
6. Prethish Sreenivas
7. Paulomi Modi
8. Xiang Ru Zhao
9. Antoine Baudin
10. Daniel G Robledo
11. Abhik Bandyopadhyay
12. Aaron Sugalski
13. Anil K Challa
14. Dias Kurmashev
15. Andrea R Gilbert
16. Gail E Tomlinson
17. Peter Houghton
18. Yidong Chen
19. Madeline N Hayes
20. Eleanor Y Chen
21. David S Libich
22. Myron S Ignatius

• Curated by eLife

  eLife Assessment:

  This manuscript sheds light on the biology of embryonal rhabdomyosarcoma, a common pediatric muscle tumor, by exploiting an established zebrafish model. Specifically, new knowledge is revealed of how the p53 tumor suppressor contributes to progression and extent of disease. This paper will be of interest not only to pediatric oncologists but also the broader cancer research community given the frequency of TP53 mutations as secondary lesions in human cancer.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Clonal transcriptomics identifies mechanisms of chemoresistance and empowers rational design of combination therapies

1. Sophia A Wild
2. Ian G Cannell
3. Ashley Nicholls
4. Katarzyna Kania
5. Dario Bressan
6. CRUK IMAXT Grand Challenge Team
7. Gregory J Hannon
8. Kirsty Sawicka

• Curated by eLife

  eLife Assessment:

  This manuscript describes a highly novel barcoding strategy for forward genetic lineage tracing of tumor cells in vitro and in the in vivo environment. The technique, coined WILDseq, can be used to track cells present in vitro which are enriched or depleted in the in vivo environment. Treatment further contributes to clonal expansion and retraction and emergence of populations with sensitivity to alternate agents. The studies are rigorously conducted and are highly impactful.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife