DLC-1 tumor suppressor regulates CD105 expression on human non-small cell lung carcinoma cells through inhibiting TGF- β1 signaling.

In this study, we revealed that the DLC-1-deficient, but not the DLC-1-competent, human non-small cell lung carcinoma cells (NSCLCs) could acquire the TGF-β1-induced expression of CD105, a common surface marker of mesenchymal stem cells, with consequent increase in CD105-associated cell motility. Interestingly, the induced CD105 expression and cell motility were subjected to the inhibition by the DLC-1-RhoA-Rock1 signaling through inhibiting the serine phosphorylation at a linker region, but not at the C-terminus, of the Smad3 protein and Smad3 protein nuclear translocation down the canonical TGF-β1 signaling. In addition, the evidence suggested that DLC-1 very likely exerted its inhibitory effects on the TGF-β1 signaling and the associated CD105 acquisition in both the cytoplasm and the nucleus. Consistent to the in vitro findings, a reverse correlation between CD105 and DLC-1 in protein expression was identified in primary NSCLC tissues and their surrounding non-tumor tissues. In summary, this study revealed a novel anti-metastasis mechanism governed by the DLC-1 tumor/metastasis suppressor, thus helping design new diagnostic and therapeutic approaches for NSCLCs. PMID: 31770531 [PubMed - as supplied by publisher]
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research