Repurposing Homoharringtonine for Thyroid Cancer Treatment Through TIMP1/FAK/PI3K/AKT Signaling Pathway

Overview

Journal iScience

Publisher Cell Press

Date 2024 May 21

PMID 38770133

Authors

Chuang Xi

Guoqiang Zhang

Nan Sun

Mengyue Liu

Nianting Ju

Chentian Shen

Hongjun Song

Quanyong Luo

Zhongling Qiu

Affiliations

Soon will be listed here.

Abstract

Homoharringtonine (HHT), an alkaloid isolated from , is an effective anti-leukemia agent and exhibits inhibitory effects in various solid tumors. However, the impacts of HHT treatment on thyroid cancer (TC) remain unclear. Our findings demonstrated that HHT exhibited remarkable anti-TC activity that involved inhibiting cell proliferation, invasion, and migration, as well as inducing apoptosis. Proteomics analysis revealed that the expression of the tissue inhibitor of metalloproteinase 1 (TIMP1) was downregulated in TC cells after HHT treatment. TIMP1 overexpression promoted TC progression and partially reversed the anti-TC effects of HHT, while TIMP1 downregulation inhibited TC progression and enhanced the anti-TC effects of HHT. Furthermore, TIMP1 re-expression attenuated the enhancement of anti-TC effects of HHT induced by TIMP1 knockdown. Mechanistically, HHT exerted anti-TC effects by downregulating TIMP1 expression and then inactivating the FAK/PI3K/AKT signaling pathway. Taken together, our study demonstrated that HHT could inhibit TC progression by inhibiting the TIMP1/FAK/PI3K/AKT signaling pathway.

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