Cancer Biology

Mutant SF3B1 promotes malignancy in PDAC

1. Patrik Simmler
2. Eleonora I Ioannidi
3. Tamara Mengis
4. Kim Fabiano Marquart
5. Simran Asawa
6. Kjong Van-Lehmann
7. Andre Kahles
8. Tinu Thomas
9. Cornelia Schwerdel
10. Nicola Aceto
11. Gunnar Rätsch
12. Markus Stoffel
13. Gerald Schwank

• Curated by eLife

  eLife assessment

  This work examines a role for altered splicing in pancreatic tumorigenesis by interrogating effects of a specific mutation in the Sf3b splicing factor in pancreatic organoid and cell line growth primarily, with some in vivo work also performed. There is significant potential in the study but there is a concern about the lack of in vivo validation of claims that are most relevant to metastatic progression and the focus on one specific mechanism at the expense of other possible effects on splicing of factors important for disease progression.

Reviewed by eLife

TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients

1. Andrea Sacconi
2. Sara Donzelli
3. Claudio Pulito
4. Stefano Ferrero
5. Francesca Spinella
6. Aldo Morrone
7. Marta Rigoni
8. Fulvia Pimpinelli
9. Fabrizio Ensoli
10. Giuseppe Sanguineti
11. Raul Pellini
12. Nishant Agrawal
13. Evgeny Izumchenko
14. Gennaro Ciliberto
15. Aldo Giannì
16. Paola Muti
17. Sabrina Strano
18. Giovanni Blandino

Reviewed by ScreenIT

Lung cancer models reveal SARS-CoV-2-induced EMT contributes to COVID-19 pathophysiology

1. C. Allison Stewart
2. Carl M. Gay
3. Kavya Ramkumar
4. Kasey R. Cargill
5. Robert J. Cardnell
6. Monique B. Nilsson
7. Simon Heeke
8. Elizabeth M. Park
9. Samrat T. Kundu
10. Lixia Diao
11. Qi Wang
12. Li Shen
13. Yuanxin Xi
14. Bingnan Zhang
15. Carminia Maria Della Corte
16. Youhong Fan
17. Kiran Kundu
18. Boning Gao
19. Kimberley Avila
20. Curtis R. Pickering
21. Faye M. Johnson
22. Jianjun Zhang
23. Humam Kadara
24. John D. Minna
25. Don L. Gibbons
26. Jing Wang
27. John V. Heymach
28. Lauren Averett Byers

Reviewed by ScreenIT

Elevated expression of ACE2 in tumor‐adjacent normal tissues of cancer patients

1. Tom Winkler
2. Uri Ben‐David

Reviewed by ScreenIT

The integration of Tgfβ and Egfr signaling programs confers the ability to lead heterogeneous collective invasion

1. Apsra Nasir
2. Sharon Camacho
3. Alec T. McIntosh
4. Garrett T. Graham
5. Raneen Rahhal
6. Molly E. Huysman
7. Fahda Alsharief
8. Anna T. Riegel
9. Gray W. Pearson

• Curated by eLife

  eLife assessment

  This represents an important study that demonstrates a high degree of heterogeneity within trailblazer cells in clusters that participate in collective migration. Solid methods highlight this heterogeneity and show that in TNBC cancers, trailblazer cells are defined by vimentin (and not Keratin 14) and are dependent on both TGFbeta and EGFR signaling.

Reviewed by eLife

Rewiring of master transcription factor cistromes during high-grade serous ovarian cancer development

1. Robbin A. Nameki
2. Heidi Chang
3. Pak Yu
4. Forough Abbasi
5. Xianzhi Lin
6. Jessica Reddy
7. Marcela Haro
8. Marcos AS Fonseca
9. Matthew L. Freedman
10. Ronny Drapkin
11. Rosario I. Corona
12. Kate Lawrenson

• Curated by eLife

  eLife assessment

  This fundamental study has successfully identified four key transcription factors (MECOM, PAX8, SOX17, and WT1) that exhibit synergistic effects and are potentially responsible for the transformation of fallopian tube secretory epithelial cells into high-grade serous 'ovarian' cancer cells. Convincing data strongly support the drawn conclusion and significantly contribute to our understanding of the etiology of this devastating cancer. The implications of this finding are substantial, as it provides molecular insights that can potentially pave the way for innovative diagnostics and therapeutics in the field of gynecological oncology. Enhancing the clarity and impact of this study would be achieved through improvements in data presentation.

Reviewed by eLife

Spatial determination and prognostic impact of the fibroblast transcriptome in pancreatic ductal adenocarcinoma

1. Wayne Croft
2. Hayden Pearce
3. Sandra Margielewska-Davies
4. Lindsay Lim
5. Samantha M Nicol
6. Fouzia Zayou
7. Daniel Blakeway
8. Francesca Marcon
9. Sarah Powell-Brett
10. Brinder Mahon
11. Reena Merard
12. Jianmin Zuo
13. Gary Middleton
14. Keith Roberts
15. Rachel M Brown
16. Paul Moss

• Curated by eLife

  eLife assessment:

  This manuscript uses an innovative combination of spatial profiling with single-cell transcriptomics to define expression profiles of stromal components in proximal tumor regions compared to those in distal regions in pancreatic ductal adenocarcinoma (PDAC). Based on this, the authors claim that the presence of a proximal fibroblast population predicts worse outcomes for PDAC patients than the presence of a distal fibroblast population. While the work provides valuable insight into how different types of tumor stromal fibroblasts may affect PDAC outcomes, the work is currently incomplete and will benefit from more extended use of fibroblast and myeloid cell markers and efforts to better define the transcriptomic data generated.

Reviewed by eLife

Single-cell profiling and zebrafish avatars reveal LGALS1 as immunomodulating target in glioblastoma

1. Lise Finotto
2. Basiel Cole
3. Wolfgang Giese
4. Elisabeth Baumann
5. Annelies Claeys
6. Maxime Vanmechelen
7. Brecht Decraene
8. Marleen Derweduwe
9. Nikolina Dubroja Lakic
10. Gautam Shankar
11. Madhu Nagathihalli Kantharaju
12. Jan Philipp Albrecht
13. Ilse Geudens
14. Fabio Stanchi
15. Keith L. Ligon
16. Bram Boeckx
17. Diether Lambrechts
18. Kyle Harrington
19. Ludo Van Den Bosch
20. Steven De Vleeschouwer
21. Frederik De Smet
22. Holger Gerhardt

Reviewed by Review Commons

Cancers adapt to their mutational load by buffering protein misfolding stress

1. Susanne Tilk
2. Judith Frydman
3. Christina Curtis
4. Dmitri Petrov

• Curated by eLife

  eLife assessment

  Tilk and colleagues present a computational analysis of tumor transcriptomes to investigate the hypothesis that the large number of somatic mutations in some tumors is detrimental such that these detrimental effects are mitigated by an up-regulation by pathways and mechanisms that prevent protein misfolding. The authors address this question by fitting a model that explains the log expression of a gene as a linear function of the log number of mutations in the tumor and show that specific categories of genes (proteasome, chaperones, ...) tend to be upregulated in tumors with a large number of somatic mutations. Some of the associations presented could arise through confounding, but overall the authors present solid evidence that mutational load is associated with higher expression of genes involved in mitigation of protein misfolding – an important finding with general implications for our understanding of cancer evolution.

Reviewed by eLife

Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer

1. José Manuel García-Martínez
2. Ana Chocarro-Calvo
3. Javier Martínez-Useros
4. María Jesús Fernández-Aceñero
5. M Carmen Fiuza
6. José Cáceres-Rentero
7. Antonio De la Vieja
8. Antonio Barbáchano
9. Alberto Muñoz
10. María Jesús Larriba
11. Custodia García-Jiménez

• Curated by eLife

  eLife assessment

  This study demonstrates that vitamin D-bound VDR increased the expression of SIRT1 and that vitamin D-bound VDR interacts with SIRT1 to cause auto-deacetylation on Lys610 and activation of SIRT1 catalytic activity. This is an important finding that is relevant to the actions of VDR on colorectal cancer. The data presented to support the presented conclusion are convincing.

Reviewed by eLife