TMCO1 regulates energy metabolism and mitochondrial function of hepatocellular carcinoma cells through TOMM20, affecting the growth of subcutaneous graft tumors and infiltration of CAFs

This study mainly shows the role of endoplasmic reticulum transmembrane and coiled coil domains 1 (TMCO1) in the regulatory mechanism of hepatocellular carcinoma (HCC). Invasion and migration capacity were detected by Transwell and Wound healing after TMCO1 and TOMM20 overexpression and knockdown. And mitochondrial function was detected through reactive oxygen species (ROS), mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (MMP) and ATP production. A model of subcutaneous tumor formation in nude mice was established to detect the effect of TMCO1 on tumor formation. The results showed that overexpression of TMCO1 significantly promoted HCC cell metastasis, promoted cell proliferation and ATP production, inhibited cell apoptosis, mPTP opening and ROS production, mediated the increase of MMP level and cytoskeletal remodeling. However, knocking down TMCO1 can have the opposite effect. More importantly, knocking down TOMM20 can block the regulation effect of TMCO1, and TOMM20 overexpression can alleviate the inhibitory effect of knocking down TMCO1 on the development of liver cancer cells. In animal models, knockdown of TMCO1 expression significantly inhibited the growth of subcutaneous implant tumors. This suggests TMCO1 may be a potential and valuable therapeutic target for liver cancer.