Cancer Biology

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

Beta human papillomavirus 8E6 promotes alternative end joining

1. Changkun Hu
2. Taylor Bugbee
3. Rachel Palinski
4. Ibukun A Akinyemi
5. Michael T McIntosh
6. Thomas MacCarthy
7. Sumita Bhaduri-McIntosh
8. Nicholas Wallace

• Curated by eLife

  Evaluation Summary:

  This manuscript reports useful data on how human papillomavirus 8E6 protein regulates DSB repair pathways in human cells. The data support the claim that 8E6 promotes alternative end-joining through binding and destabilizing the p300 acetyltransferase, but the study remains relatively descriptive and incomplete as it is not yet clear which alternative end-joining pathway is involved lacking a test of a direct involvement of DNA polymerases theta (POLθ).

  (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

FOXP2 confers oncogenic effects in prostate cancer

1. Xiaoquan Zhu
2. Chao Chen
3. Dong Wei
4. Yong Xu
5. Siying Liang
6. Wenlong Jia
7. Jian Li
8. Yanchun Qu
9. Jianpo Zhai
10. Yaoguang Zhang
11. Pengjie Wu
12. Qiang Hao
13. Linlin Zhang
14. Wei Zhang
15. Xinyu Yang
16. Lin Pan
17. Ruomei Qi
18. Yao Li
19. Feiliang Wang
20. Rui Yi
21. Ze Yang
22. Jianye Wang
23. Yanyang Zhao

• Curated by eLife

  Evaluation Summary:

  The authors identify a new FOXP2-CPED1 gene fusion in prostate cancer that leads to the increased expression of FOXP2 and subsequent transformation of non-cancer cells. Increased FOXP2 was shown to promote prostate cancer in part through the increased expression and activation of the receptor tyrosine kinase MET, a known driver of prostate cancer. Notably, the authors created new genetically engineered mouse models of FOXP2 and FOXP2-CPED1 overexpression in prostate luminal epithelial cells which was sufficient to cause prostatic intraepithelial neoplasia in these mice with lesions that confirmed increased MET signaling. Oncogenes are typically interesting drug targets or interact with possible drug targets, and the manuscript could thus have a significant societal impact on better understanding drivers of the disease.

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

SHARPIN S146 phosphorylation mediates ARP2/3 interaction, cancer cell invasion and metastasis

1. Umar Butt
2. Meraj H. Khan
3. Jeroen Pouwels
4. Jukka Westermarck

Reviewed by Review Commons