TMEM165, a Golgi transmembrane protein, is a novel marker for hepatocellular carcinoma and its depletion impairs invasion activity

다국어 초록 (Multilingual Abstract)

<P>Transmembrane protein 165 (TMEM165), a Golgi protein, functions in ion homeostasis and vesicular trafficking in the Golgi apparatus. While mutations in <I>TMEM165</I> are known to cause human ‘congenital disorders of glycosylation’, a recessive autosomal metabolic disease, the potential association of this protein with human cancer development has not been explored to date. In the present study, we revealed that <I>TMEM165</I> is overexpressed in HCC and its depletion weakens the invasive activity of cancer cells through suppression of matrix metalloproteinase-2 (MMP-2) expression. Levels of <I>TMEM165</I> mRNA and protein were clearly increased in HCC patient tissues and cell cultures. Quantitative real-time RT-PCR analysis of fresh HCC tissues (n=88) revealed association of <I>TMEM165</I> overexpression with more frequent macroscopic vascular invasion, microscopic serosal invasion and higher α-fetoprotein levels. Notably, depletion of <I>TMEM165</I> led to a marked decrease in the invasive activity of two different HCC cell types, Huh7 and SNU475, accompanied by downregulation of MMP-2. Our collective findings clearly indicated that TMEM165 contributed to the progression of HCC by promoting invasive activity, supporting its utility as a novel biomarker and therapeutic target for cancer.</P>