Cancer Biology

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 A 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

Comprehensive characterization of tumor microenvironment in colorectal cancer via molecular analysis

1. Xiangkun Wu
2. Hong Yan
3. Mingxing Qiu
4. Xiaoping Qu
5. Jing Wang
6. Shaowan Xu
7. Yiran Zheng
8. Minghui Ge
9. Linlin Yan
10. Li Liang

• Curated by eLife

  eLife assessment

  This study represents a valuable body of work in which the authors assemble a molecular description of colorectal cancer and classification into subtypes. Overall, the evidence supporting the findings is solid and could be improved with more detail. Consensus over a diverse range of data from publicly available sources is convincing. When added to existing knowledge this work may contribute to future biomarker discoveries for colorectal cancer.

Reviewed by eLife

Inhibitors of Rho kinases (ROCK) induce multiple mitotic defects and synthetic lethality in BRCA2-deficient cells

1. Julieta Martino
2. Sebastián Omar Siri
3. Nicolás Luis Calzetta
4. Natalia Soledad Paviolo
5. Cintia Garro
6. Maria F Pansa
7. Sofía Carbajosa
8. Aaron C Brown
9. José Luis Bocco
10. Israel Gloger
11. Gerard Drewes
12. Kevin P Madauss
13. Gastón Soria
14. Vanesa Gottifredi

• Curated by eLife

  eLife assessment

  The authors have uncovered a new target that may be exploited to selectively kill BRCA2 mutant cancer cells. Strengths of the study include the novel pathway uncovered (ROCK kinases) and the strong data in support of the findings. Weaknesses include limited detail regarding the mechanism of BRCA2-specific cell death by ROCK kinase inhibitors, limited information on why some ROCK kinase inhibitors are not effective, as well as whether the cell killing in BRCA2 wild-type cells by ROCK kinase inhibitors is the same mechanism but just attenuated. The work will be of interest to cancer biologists and colleagues studying kinases.

Reviewed by eLife

Proteomic characteristics reveal the signatures and the risks of T1 colorectal cancer metastasis to lymph nodes

1. Aojia Zhuang
2. Aobo Zhuang
3. Yijiao Chen
4. Zhaoyu Qin
5. Dexiang Zhu
6. Li Ren
7. Ye Wei
8. Pengyang Zhou
9. Xuetong Yue
10. Fuchu He
11. Jianmin Xu
12. Chen Ding

• Curated by eLife

  eLife assessment

  This is an important contribution to colorectal cancer research to understand how we can predict high-risk patients for recurrence. The strength of the evidence is solid and looks at a novel approach but an approach that still has opportunities to improve.

Reviewed by eLife