한빛사논문
- 조회357
Alexander T Bahcheli 1,2,9, Hyun-Kee Min 2,3,4,9, Masroor Bayati 1,5, Hongyu Zhao 3,4,6, Alexander Fortuna 1, Weifan Dong 2,3,4, Irakli Dzneladze 1, JadeChan 2,3,4, XinChen 3,4,7, Kissy Guevara-Hoyer 1,8, Peter B Dirks 2,3,4, Xi Huang 2,3,4,* & Jüri Reimand 1,2,5,*
1Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada.
2Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
3Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
4Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
5Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
6Department of Neurosurgery and Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, Hunan, China.
7Songjiang Research Institute,Songjiang Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
8Cancer Immunomonitoring and Immuno-Mediated Pathologies Support Unit,Department of Clinical Immunology, Institute of Laboratory Medicine (IML) and Biomedical Research Foundation (IdiSCC), San Carlos Clinical Hospital, Madrid, Spain.
9These authors contributed equally: Alexander T Bahcheli, Hyun-Kee Min.
*Corresponding authors: correspondence to Xi Huang or Jüri Reimand
Abstract
Ion channels, transporters, and other ion-flux controlling proteins, collectively comprising the “ion permeome”, are common drug targets, however, their roles in cancer remain understudied. Our integrative pan-cancer transcriptome analysis shows that genes encoding the ion permeome are significantly more often highly expressed in specific subsets of cancer samples, compared to pan-transcriptome expectations. To enable target selection, we identified 410 survival-associated IP genes in 33 cancer types using a machine-learning approach. Notably, GJB2 and SCN9A show prominent expression in neoplastic cells and are associated with poor prognosis in glioblastoma, the most common and aggressive brain cancer. GJB2 or SCN9A knockdown in patient-derived glioblastoma cells induces transcriptome-wide changes involving neuron projection and proliferation pathways, impairs cell viability and tumor sphere formation in vitro, perturbs tunneling nanotube dynamics, and extends the survival of glioblastoma-bearing mice. Thus, aberrant activation of genes encoding ion transport proteins appears as a pan-cancer feature defining tumor heterogeneity, which can be exploited for mechanistic insights and therapy development.
논문정보
- Research article
- 2024년 01월 (BRIC 등록일 2024-02-08)
- 국외 연구진
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