Irisin, an exercise myokine, potently suppresses tumor proliferation, invasion, and growth in glioma
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Journal Volume
34
Journal Issue
7
Pages
9678
Date Issued
2020-07
Author(s)
Huang, Chiun-Wei
Chang, Yu-Hsuan
Lee, Hsuan-Hung
Wu, Jing-Yi
Huang, Jia-Xing
Chung, Yi-Hsiu
Hsu, Shih-Ting
Wei, Kuo-Chen
Abstract
Glioblastoma multiforme is the most common and aggressive glial tumor with poor prognosis. Importantly, effective treatment options for glioblastoma are unmet needs. Obesity and low physical activity have been linked with a high risk of cancer, and exercise is related to delayed cancer development and progression. Epidemiological studies have revealed a correlation between exercise and the survival rate of patients with glioblastoma. Nevertheless, the mechanisms by which exercise exerts its anticancer effects in glioblastoma remain unclear. Here, we found that irisin, an exercise-induced myokine, induced G2 /M cell cycle arrest and increased p21 levels in glioblastoma cells, leading to the inhibition of cell proliferation. In addition, irisin inhibited glioblastoma cell invasion by upregulating TFPI-2 and even reversed the aggressive tumor phenotype promoted by co-cultivation with cancer-associated adipocytes. Furthermore, irisin retarded xenograft glioblastoma tumor growth, and radiolabeled irisin demonstrated specific tumor-targeting capability in vivo. Therefore, this study identified one potential molecular mechanism by which exercise prevents cancer progression via irisin. Intriguingly, irisin has the potential to be developed as a molecular imaging and therapeutic anticancer agent.
Subjects
TFPI-2; cell invasion; exercise; glioblastoma; irisin; tumor targeting
SDGs
Other Subjects
irisin; protein p21; antineoplastic agent; fibronectin; FNDC5 protein, human; myokinin; neuropeptide; 3T3-L1 cell line; adipocyte; animal experiment; Article; cancer growth; cell invasion; cell proliferation; coculture; controlled study; G2 phase cell cycle checkpoint; glioblastoma; in vivo study; LN-18 cell line; M phase cell cycle checkpoint; male; mouse; nonhuman; priority journal; radiolabeling; T98G cell line; tumor xenograft; upregulation; animal; apoptosis; cell cycle; cell motion; cell proliferation; drug screening; exercise; glioma; human; metabolism; nude mouse; pathology; tumor cell culture; tumor invasion; Animals; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Movement; Cell Proliferation; Exercise; Fibronectins; Glioma; Humans; Male; Mice; Mice, Nude; Neoplasm Invasiveness; Neuropeptides; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
Publisher
WILEY
Type
journal article