T‑cell immunoglobulin mucin‑3 as a potential inducer of the epithelial‑mesenchymal transition in hepatocellular carcinoma

Abstract

T-cell immunoglobulin mucin (TIM)-3 is an important member of the TIM gene family, which was thought to contribute to the progression of numerous types of cancer, including hepatocellular carcinoma (HCC); however, the mechanism underlying TIM-3 functions in HCC progression has not yet been extensively investigated. The present study aimed to investigate the function of TIM-3 in the metastasis of HCC and to determine whether the alteration of TIM-3 expression levels regulated the epithelial-mesenchymal transition (EMT) occurrence of HCC, using epithelial (E)-cadherin, neuronal (N)-cadherin, matrix metallopeptidase-9 (MMP-9), Twist 1, Slug, Snail, and Smad as EMT biomarkers. The results demonstrated that upregulation of TIM-3 using TIM-3 lentiviral activation particles (5 µl) increased cell migration and invasion, which was decreased in TIM-3 short interfering RNA-infected cells (10 µM, 3 µl) correspondingly. SMMC-7721 HCC cells were used as the control. EMT was aggravated in TIM-3 upregulated SMMC-7721 cells, which was attenuated in the TIM-3 interference group, accompanied by an alteration of E-cadherin, N-cadherin, MMP-9, Twist 1, Slug, Snail and Smad expression levels. The data presented suggests that TIM-3 serves an essential role in the metastasis of HCC, the mechanism of which was associated with EMT occurrence. Interference of TIM-3 is expected to be an effective means to prevent and control EMT, and further the metastasis of HCC.

The Role of Matrix Metalloproteinases in the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma

“…EMT is a biological process defined as a rigorously programmed shift from epithelial to mesenchymal cell features that plays a substantial role in embryogenesis and organ development and also tissue repair and regeneration, as well as tumor invasion and metastasis [27]. EMT is triggered and sustained by multiple molecular processes, which, in some cases, may be used as biomarkers.…”

Cell Surface Proteins in Hepatocellular Carcinoma: From Bench to Bedside

“…Lin et al reported a role of the T cell immunoglobulin and mucin-domain containing-3 (Tim-3) in regulating EMT occurrence and further metastasis of HCC in vitro [127]. As recently extensively reviewed by Liu et al, Tim-3 is a new discovered immune checkpoint molecule playing a relevant role in the development of HCC [128].…”

Tim-3 expression and its role in hepatocellular carcinoma

“…A further mechanistic study [ 54 ] showed that tumor cell-intrinsic Tim-3 would promote HCC development by triggering auto-secretion of IL-6 and then accelerating tumor growth through the STAT3 signaling pathway. Moreover, overexpression of Tim-3 by introducing its lentiviral-expressing particles in SMMC-7721 cell line promoted cell migration and invasion by facilitating the epithelial-mesenchymal transition (EMT) [ 55 ]. These studies indicate that Tim-3 expression in HCC cells accelerates tumor growth through auto-secretion of IL-6 and enhanced metastatic ability of HCC cells by promoting EMT.…”