A tumor suppressor DLC1: The functions and signal pathways

Abstract

Deleted in liver cancer‐1 (DLC1), a potential tumor suppressor, acts as a GTPase‐activating protein for Rho family members. In many human cancers, the DLC1 expression is frequently downregulated or inactivated, which allows cancer cells to proliferate and disseminate. In this review, we describe the characteristics and other members of the DLC1 family and delineate the signal pathways DLC1 involved in regulating cancer cell growth, colony formation, apoptosis, senescence, autophagy, migration and invasion. In addition, we explore the clinical data of DLC1 and the mechanisms that natural products upregulate the DLC1 expression to inhibit cancer. Despite these insights, many important unanswered questions remain about the exact mechanisms of DLC1‐mediated cancer suppression.

Comparison of Stage 4 and Stage 4s Neuroblastoma Identifies Autophagy-Related Gene and LncRNA Signatures Associated With Prognosis

“…Two of them (ULK1 and ARNT) have been found to have important roles in regulating neuronal development: ULK1 is essential to mediate autophagy under nutrient-deficient conditions and regulate axon guidance in the developing forebrain of mouse via a non-canonical pathway (34,35); ARNT is mostly expressed in neuronal cell types and play roles in regulating dendritic morphology and neuronal differentiation (36). Two of them (GABARAPL1 and DLC1) have been found to have a tumorsuppressive function: the GABARAPL1 protein could positively regulate ULK1 activity and autophagosome formation (37) and was also found to have a tumor-suppressive function in breast cancer cells (38,39); DLC1 is involved in regulating autophagy and apoptosis and was found to be a potential tumor suppressor in many types of human cancers (40). ATG4 is the only protease functions as an important factor in the ATG8 conjugation system, and its activity is essential to autophagy (41).…”

Dysregulation of Rho GTPases in Human Cancers

“…In contrast to RhoGEFs, certain RhoGAPs, including those deleted in liver cancer (DLC-1) and p190RhoGAP, are reportedly generally downregulated in various cancers. Reduced DLC-1 expression through genomic deletion or epigenetic silencing is often observed in hepatocellular and cervical carcinoma [94][95][96]. The knockdown of DLC-1 increases GTP-bound RhoA and tumorigenic growth, and expression of constitutively active RhoA in these cells accelerate liver tumor formation, suggesting that DLC-1 acts as tumor suppressor [94].…”

Germline and somatic mutations in the pathology of pineal cyst: A whole‐exome sequencing study of 93 individuals

“…In addition, RB1 is a tumor suppressor gene and plays significant role in cancer biology (Dyson, 2016;Knudsen et al, 2020). Interestingly, we targeted DLC1, a tumor suppressor gene (Zhang & Li, 2020), from our five most frequently mutated genes in the gene-based analysis (Table S4). DLC1 encodes a GTPase-activating protein which is one of the Rho family members (Zhang & Li, 2020).…”

“…Interestingly, we targeted DLC1, a tumor suppressor gene (Zhang & Li, 2020), from our five most frequently mutated genes in the gene-based analysis (Table S4). DLC1 encodes a GTPase-activating protein which is one of the Rho family members (Zhang & Li, 2020). In multiple cancers, expression level of DLC1 is downregulated which leads to the continual unregulated cell proliferation, migration and invasion (Jensch et al, 2018;Wang et al, 2020;Wu et al, 2018).…”