Lipogenesis promotes mitochondrial fusion and maintains cancer stemness in human NSCLC

Cancer stem-like cells (CSCs) are critically involved in cancer metastasis and chemoresistance, acting as one major obstacle in clinical practice. While accumulating studies have implicated the metabolic reprogramming of CSCs, mitochondrial dynamics in such cells remain poorly understood. Here we pi...

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Bibliographic Details
Published in:JCI insight 2023-03, Vol.8 (6)
Main Authors: Liu, Zhen, Lei, Jiaxin, Wu, Tong, Hu, Weijie, Zheng, Ming, Wang, Ying, Song, Jingdong, Ruan, Hang, Xu, Lin, Ren, Tao, Xu, Wei, Wen, Zhenke
Format: Article
Language:English
Subjects:
Carcinoma, Non-Small-Cell Lung - pathology
Humans
Lipogenesis - genetics
Lung Neoplasms - pathology
Mitochondrial Dynamics
Oncology
Transcription Factors - metabolism
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Summary:Cancer stem-like cells (CSCs) are critically involved in cancer metastasis and chemoresistance, acting as one major obstacle in clinical practice. While accumulating studies have implicated the metabolic reprogramming of CSCs, mitochondrial dynamics in such cells remain poorly understood. Here we pinpointed OPA1hi with mitochondrial fusion as a metabolic feature of human lung CSCs, licensing their stem-like properties. Specifically, human lung CSCs exerted enhanced lipogenesis, inducing OPA1 expression via transcription factor SAM Pointed Domain containing ETS transcription Factor (SPDEF). In consequence, OPA1hi promoted mitochondrial fusion and stemness of CSCs. Such lipogenesishi, SPDEFhi, and OPA1hi metabolic adaptions were verified with primary CSCs from lung cancer patients. Accordingly, blocking lipogenesis and mitochondrial fusion efficiently impeded CSC expansion and growth of organoids derived from patients with lung cancer. Together, lipogenesis regulates mitochondrial dynamics via OPA1 for controlling CSCs in human lung cancer.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.158429