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

Sep 23, 2026

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Hepatocellular carcinoma (HCC) is highly invasive and has poor prognosis, so identifying key driver genes is essential. TLCD1, a TLC-domain family member involved in membrane trafficking and lipid metabolism regulation, is predicted to be abnormally expressed in HCC, but its function is unclear. Integrating transcriptome analysis and immunohistochemical detection shows TLCD1 upregulation in tumor tissues, where high expression shortens overall and disease-free survival. Knockdown and overexpression cell models demonstrate effects on proliferation and metastasis, and mechanistic data suggest ERK activation via KRAS/ERK1/2 and c-MYC phosphorylation, supporting TLCD1 as a potential prognostic biomarker and therapeutic target.

LanguageEnglish

CategoryHealthcare

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Pages17

Reading Time43 min

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TLCD1 and malignant progression in hepatocellular carcinoma

Rationale and clinical significance

TLCD1 expression and patient survival association

Functional validation in cell models

Mechanistic link to MAPK/ERK signaling

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN TLCD1 correlates with malignant progression of hepatocellular carcinoma and activation of the ERK signaling cascade Pei Wen1,4, Qiuyan Liu1,4, Xuefeng Guo1,2, Chao Tan1,2, Xiaonian Zhu1,2, Xiaofei Li1,2, Yuanxiao Du1, Qibin Zhang1, Lingyun Liu3􀀍 & Chunhua Bei1,2􀀍 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 ofTLCD1 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 ofTLCD1 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. Keywords TLCD1, Hepatocellular carcinoma, ERK signaling pathway, Malignant progression, Cell proliferation Abbreviations RT PBS DEGs OSDFSKEGG GOIHC RT-qPCRCCK-8 WTTLCD1-SH1 KDNC TLCD1-OE OENC Room Temperature Phosphate Buffered Saline Differentially Expressed Genes Overall Survival Disease Free Survival Kyoto Encyclopedia of Genes and Genomes Gene Ontology Immunohistochemistry Reverse Transcription Quantitative PCR Cell Counting Kit-8 Wild Type TLCD1-knockdown Knockdown Negative Control TLCD1-overexpression Room Temperature 1Department of Epidemiology and Health Statistics, School of Public Health, Guilin Medical University, Guilin 541199, Guangxi, China. 2Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, School of Public Health, Guilin Medical University, Guilin 541199, Guangxi, China. 3Department of Hepatobiliaryand Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, China. 4Pei Wen and Qiuyan Liu contributed equally to this work. 􀀍 email: [allllyy@163.com](allllyy@163.com); [chunhuabei@glmc.edu.cn](chunhuabei@glmc.edu.cn) GDC Genomic Data Commons MHV Middle Hepatic Vein Hepatocellular carcinoma (HCC) is the predominant subtype of primary liver cancer, accounting for 75– 85% of all cases1. Its global incidence and mortality have risen steadily, making it the third leading cause of cancer-related death2,3. Recent epidemiological data estimate approximately 367,700 new cases and 317,000 deaths from primary liver cancer each year, ranking fourth for incidence and second for mortality among all malignancies4. The complex pathogenesis of HCC is largely due to its high level of heterogeneity and lack of symptoms during the early stages, which often leads to diagnosis at an advanced phase, as well as its strong propensity for progression to metastatic and recurrent disease5,6. Despite optimized treatment strategies for HCC—including liver transplantation, local ablation therapy, transarterial chemoembolization, and the use of novel targeted drugs—the disease still has a poor prognos

FAQs

What is the main goal of the study regarding TLCD1 in HCC?

To investigate TLCD1 expression patterns, its biological functions, and the potential molecular mechanism driving hepatocellular carcinoma progression.

How does TLCD1 expression relate to patient outcomes in HCC?

TLCD1 is significantly upregulated in HCC tissues, and high expression is associated with shortened overall survival and disease-free survival.

What cellular effects are observed when TLCD1 is overexpressed or knocked down?

Overexpression promotes HCC cell proliferation and metastasis, while TLCD1 knockdown inhibits these malignant behaviors in cell model assays.

Which signaling pathway is implicated in the mechanism of TLCD1-driven malignancy?

TLCD1 appears to activate the MAPK/ERK signaling cascade by increasing phosphorylation of KRAS, ERK1/2, and c-MYC.

Sep 23, 2026

Uploaded by awa