Cancer Biology

VGLL2 and TEAD1 fusion proteins drive YAP/TAZ-independent transcription and tumorigenesis by engaging p300

1. Susu Guo
2. Xiaodi Hu
3. Jennifer L. Cotton
4. Lifang Ma
5. Qi Li
6. Jiangtao Cui
7. Yongjie Wang
8. Ritesh P. Thakare
9. Zhipeng Tao
10. Y. Tony Ip
11. Xu Wu
12. Jiayi Wang
13. Junhao Mao

• Curated by eLife

  eLife assessment

  In this valuable study, Gue, Hue et al. describe how two poorly understood rhabdomyosarcoma fusion-oncogenes, VGLL2::NCOA2 and TEAD1::NCOA2, function at the genomic, transcriptional, and proteomic levels in multiple systems. They generated solid data that support that these fusion-oncogenes leverage TEAD transcriptional signatures, in a mechanism that is independent of YAP/TAZ, and that this activity potentially contributes to tumorigenesis. This work offers new mechanistic insights into oncogenic gene fusion events identified in cancer patients and reveals potential therapeutic strategies for the treatment of rhabdomyosarcomas.

Reviewed by eLife

Netrin signaling mediates survival of dormant epithelial ovarian cancer cells

1. Pirunthan Perampalam
2. James I MacDonald
3. Komila Zakirova
4. Daniel T Passos
5. Sumaiyah Wasif
6. Yudith Ramos-Valdes
7. Maeva Hervieu
8. Patrick Mehlen
9. Rob Rottapel
10. Benjamin Gibert
11. Rohann JM Correa
12. Trevor G Shepherd
13. Frederick A Dick

• Curated by eLife

  eLife assessment

  The authors further corroborated their model that Netrin signaling promotes survival and dissemination of non-proliferating ovarian cancer cells. These valuable results were found to be of significant potential interest to cancer biologists in as much as they address gaps in knowledge pertinent to the mechanisms underpinning ovarian cancer spread. In general, it was thought that solid experimental evidence was provided to support the role of Netrin signaling in fueling ovarian cancer progression.

Reviewed by eLife

Elevated FOXG1 supports exit from quiescence in neural stem cells through FoxO6

1. Kirsty M Ferguson
2. Carla Blin
3. Claudia Garcia-Diaz
4. Harry Bulstrode
5. Raul Bardini Bressan
6. Katrina McCarten
7. Steven M. Pollard

Reviewed by Review Commons

Tissue-resident NK cells support survival in pancreatic cancer through promotion of cDC1-CD8T activity

1. Simei Go
2. Constantinos Demetriou
3. Giampiero Valenzano
4. Sophie Hughes
5. Simone Lanfredini
6. Helen Ferry
7. Edward Arbe-Barnes
8. Shivan Sivakumar
9. Rachael Bashford-Rogers
10. Mark R. Middleton
11. Somnath Mukherjee
12. Jennifer Morton
13. Keaton Jones
14. Eric O’Neill

• Curated by eLife

  eLife assessment

  This valuable manuscript provides an interesting account documenting the role of resident CD56(br) NK cells in driving interaction with dendritic cells that attract CD8+ T cells to the pancreas cancer tumor microenvironment (TME). The work convincingly illustrates how irradiation combined with CCR5i and PD1 blockade leads to a reduction in pancreatic cancer growth that correlates with a reduction in Treg cells and enhancement of NK and CD8 T cells in the TME. The correlation of NKC1 signature with survival in pancreatic cancer patients is indeed of broader interest regarding potential relevance to other types of cancer.

Reviewed by eLife

Establishing the foundations for a data-centric AI approach for virtual drug screening through a systematic assessment of the properties of chemical data

1. Allen Chong
2. Ser-Xian Phua
3. Yunzhi Xiao
4. Woon Yee Ng
5. Hoi Yeung Li
6. Wilson Wen Bin Goh

• Curated by eLife

  eLife assessment

  This study presents a valuable finding on how data quality and data representation are key to obtain predictive machine learning models, even without resorting to complex machine learning approaches. The evidence supporting the claims of the authors is, however, incomplete, as their conclusions are drawn from a single dataset of big size, similarity analysis within and between subsets is lacking, and there are concerns regarding the composition of the training and holdout sets (active:inactive ratio, possible triviality of decoys). If the results were expanded to other quality datasets of different compositions to demonstrate robustness, the manuscript would be of wide interest in the machine learning and drug discovery fields

Reviewed by eLife

A syngeneic spontaneous zebrafish model of tp53-deficient, EGFRvIII, and PI3KCAH1047R-driven glioblastoma reveals inhibitory roles for inflammation during tumor initiation and relapse in vivo

1. Alex Weiss
2. Cassandra D'Amata
3. Bret J Pearson
4. Madeline N Hayes

• Curated by eLife

  eLife assessment

  This study presents a valuable syngeneic zebrafish model for studying glioblastoma and will be of interest to neuro-oncologists and cancer biologists. Using a feasible in vivo model to study the tumour microenvironment, cell/cell interaction, and immunity, the data are compelling, and opens up new lines of inquiries for future investigation on the impact of efferocytosis on tumor progression and cell of origin in this model as well as assessments of drug resistance mechanisms, using inhibitors to MAPK , Akt and/or mTOR pathway.

Reviewed by eLife

RBM7 deficiency promotes breast cancer metastasis by coordinating MFGE8 splicing switch and NF-kB pathway

1. Fang Huang
2. Zhenwei Dai
3. Jinmiao Yu
4. Kainan Wang
5. Chaoqun Chen
6. Dan Chen
7. Jinrui Zhang
8. Jinyao Zhao
9. Mei Li
10. Wenjing Zhang
11. Xiaojie Li
12. Yangfan Qi
13. Yang Wang

• Curated by eLife

  eLife assessment

  This study presents a rather valuable finding on the RBM7 function in spicing regulation and uncharacterized role of MFGE8 splicing alteration in breast cancer metastasis. The evidence supporting the claims of the authors is solid. The work will be of broad interest to clinicians, medical researchers and scientists working on breast cancer.

Reviewed by eLife

Prognostic Significance of preoperative serum CA125, CA19-9, CA72-4, CEA, and AFP in Patients with Endometrial cancer

1. Zi-hao Wang
2. Yun-zheng Zhang
3. Shu-wen Ge
4. Luhe-Shan
5. Bo Wang
6. Zi-yu Zhang
7. Qi-jun Wu
8. Xiao-xin Ma

• Curated by eLife

  eLife assessment

  This study presents a valuable finding on prognostic values of serum CA125, CEA, and AFP for predicting patient outcomes of endometrial cancer. The evidence supporting the claims of the authors is solid, although inclusion of detailed discussion of present results with prior documented findings would have strengthened the study. The work will be of interest to scientists working on endometrial cancer.

Reviewed by eLife

Emerging role of oncogenic ß-catenin in exosome biogenesis as a driver of immune escape in hepatocellular carcinoma

1. Camille Dantzer
2. Justine Vaché
3. Aude Brunel
4. Isabelle Mahouche
5. Anne-Aurélie Raymond
6. Jean-William Dupuy
7. Melina Petrel
8. Paulette Bioulac-Sage
9. David Perrais
10. Nathalie Dugot-Senant
11. Mireille Verdier
12. Barbara Bessette
13. Clotilde Billottet
14. Violaine Moreau

• Curated by eLife

  eLife assessment

  Hepatocellular carcinoma (HCC) is a particularly aggressive form of cancer, with an increasing number of treatment options approved for use in patients over the past decade. However, the biology of HCC and identifiable therapeutic targets have not been as clear, even in the era of molecular oncology. Likewise, the cellular biology of HCC, including the role of intercellular communication, has not been well elucidated. In this compelling study, Dantzer et al. provide fundamental insight into the role of beta-catenin on intercellular communication occurring via extracellular vesicles, with implications for immune evasion in a cancer increasingly being treated using immuno-oncologic agents.

Reviewed by eLife

Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition

1. Laleh S. Arabanian
2. Jenni Adamsson
3. Anke Unger
4. Raffaella Di Lucrezia
5. Tim Bergbrede
6. Arghavan Ashouri
7. Erik Larsson
8. Peter Nussbaumer
9. Bert M. Klebl
10. Lars Palmqvist
11. Claes M. Gustafsson

• Curated by eLife

  eLife assessment

  This solid study assesses a novel mitochondrial inhibitor in combination with the BCL-2 inhibitor venetoclax, with the aim to increase its activity in acute myeloid leukemia. It provides valuable findings of combinatorial efficacy using preclinical models, confirming the overall importance of targeting oxidative phosphorylation to overcome venetoclax resistance in acute myeloid leukemia, and could be strengthened through mechanistic studies demonstrating drug specificity, pharmacodynamic efficacy studies in vivo to test clinical utility and extended statistical analyses of the results. The study is of interest to hematologists because it addresses a key biomedical issue in acute myeloid leukemia (venetoclax resistance) and provides data regarding the safety and activity of a novel inhibitor of the mitochondrial polymerase addressed in combination with venetoclax.

Reviewed by eLife