Irisin’s Dual Role in Malignant Tumors and Its Potential as a Biomarker and Therapeutic Target

Liqun Mo,1,2,* Xu Zeng,1,* Yu Liu,1 Jin Zhang,3 Li Liu,1,2 Yingying Zhang,1 Yiping Bai1 1Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 3Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, 39216, USA*These authors contributed equally to this workCorrespondence: Yiping Bai, Department of Anesthesiology, Affiliated Hospital of Southwest Medical University, Taiping Street, Luzhou, 646000, People’s Republic of China, Tel +8618982797213, Email [email protected] Yingying Zhang, Email [email protected]: Irisin, a myokine secreted by skeletal muscle, has garnered significant attention for its multifaceted physiological roles and emerging potential as both a biomarker and therapeutic target in oncology. This review consolidates current understanding of irisin’s impact across various malignancies, focusing on its complex regulation of tumorigenesis through interactions with key signaling pathways including PI3K/AKT, AMPK-mTOR, and STAT3/Snail. Critically, irisin exhibits a paradoxical dual role: it suppresses proliferation, migration, and invasion in cancers such as lung, breast, and pancreatic carcinoma, yet paradoxically promotes the progression of hepatocellular carcinoma. This tissue-specific dichotomy presents a significant therapeutic challenge. Furthermore, inconsistent findings regarding irisin expression levels even within the same tumor type highlight the urgent need for further mechanistic investigation. Future research must prioritize elucidating the context-dependent mechanisms of irisin within the tumor microenvironment and rigorously evaluating its clinical utility as a biomarker through large-scale trials. Resolving these contradictions is essential for developing a unified understanding of irisin’s role in cancer biology. Such insights hold promise for paving the way toward novel therapeutic strategies, potentially enhancing the efficacy of personalized cancer therapy. Keywords: irisin, malignant tumors, biomarkers, therapeutic target, signaling pathways, epithelial-mesenchymal transition