TLCD1 correlates with malignant progression of hepatocellular carcinoma and activation of the ERK signaling cascade.

Hepatocellular carcinoma (HCC) is characterized by high invasiveness and poor prognosis, making the identification of key driver genes crucial for the development of effective treatment strategies. TLCD1 is a member of the TLC domain family, which participates in membrane trafficking and lipid metabolism regulation. While bioinformatics suggests that TLCD1 is abnormally expressed in HCC, experimental evidence for its functions and mechanisms is still lacking. This study aimed to explore the expression pattern, biological functions, and potential molecular mechanism of TLCD1 in HCC. By integrating transcriptome analysis and immunohistochemical detection, it was found that TLCD1 was significantly upregulated in HCC tissues, and its high expression was associated with shortened overall and disease‑free survival in HCC patients. With TLCD1 knockdown and overexpression cell models, CCK‑8, colony formation, wound healing, and transwell assays revealed that overexpression of TLCD1 significantly promoted HCC cell proliferation and metastasis, whereas TLCD1 knockdown exerted an inhibitory effect. Mechanistically, transcriptome data together with western blot analysis indicated that TLCD1 may activate the mitogen‑activated protein kinase (MAPK)/ERK signaling cascade by upregulating the phosphorylation levels of KRAS, ERK1/2, and c‑MYC. In conclusion, TLCD1 may drive the malignant progression of HCC by activating the ERK signaling pathway and may serve as a potential prognostic biomarker and therapeutic target for HCC.