TY  - EJOU
AU  - ZHANG, XINFENG 
AU  - LI, SHUANG 
AU  - SONG, MEIRU 
AU  - CHEN, YUE 
AU  - CHANG, LIANGZHENG 
AU  - LIU, ZHERUI 
AU  - DAI, HONGYUAN 
AU  - WANG, YUTAO 
AU  - YANG, GANGQI 
AU  - JIANG, YUN 
AU  - LU, YINYING 

TI  - Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma
T2  - Oncology Research

PY  - 2024
VL  - 32
IS  - 4
SN  - 1555-3906

AB  - Liver cancer is a prevalent malignant cancer, ranking third in terms of mortality rate. Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer. Hepatocellular carcinoma (HCC) has low expression of focal adhesion kinase (FAK), which increases the risk of metastasis and recurrence. Nevertheless, the efficacy of FAK phosphorylation inhibitors is currently limited. Thus, investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis. This study examined the correlation between FAK expression and the prognosis of HCC. Additionally, we explored the impact of FAK degradation on HCC metastasis through wound healing experiments, transwell invasion experiments, and a xenograft tumor model. The expression of proteins related to epithelial-mesenchymal transition (EMT) was measured to elucidate the underlying mechanisms. The results showed that FAK PROTAC can degrade FAK, inhibit the migration and invasion of HCC cells <i>in vitro</i>, and notably decrease the lung metastasis of HCC <i>in vivo</i>. Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited. Consequently, degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis, holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.
KW  - Hepatocellular carcinoma (HCC); Focal adhesion kinase (FAK); Proteolytic targeting chimera technology (PROTAC); Epithelial-mesenchymal transformation (EMT); Metastasis

DO  - 10.32604/or.2024.046231