High expression of G-protein signaling modulator 2 in hepatocellular carcinoma facilitates tumor growth and metastasis by activating the PI3K/AKT signaling pathway

Abstract

The aim of this study was to investigate the role of G-protein signaling modulator 2 in the carcinogenesis and progression of hepatocellular carcinoma. We previously showed that G-protein signaling modulator 2 was upregulated in hepatitis B virus-related hepatocellular carcinoma tissues through a hierarchical clustering analysis. With this study, we first assessed the expression pattern of G-protein signaling modulator 2 in hepatocellular carcinoma specimens and adjacent noncancerous tissues; clinical data were analyzed, along survival times, utilizing the Kaplan-Meier method. Moreover, the functions of G-protein signaling modulator 2 were examined using small-interfering RNAs in vitro. The results showed that G-protein signaling modulator 2 was clearly overexpressed in hepatocellular carcinoma tissues and cell lines and that the G-protein signaling modulator 2 expression level was related to tumor size and hepatitis B virus infection. Furthermore, G-protein signaling modulator 2 knockdown studies suggested that G-protein signaling modulator 2 accelerates cell growth, cell cycle, migration, and invasion and inhibits apoptosis, acting as an oncogene in hepatocellular carcinoma. Western blotting indicated that silencing of G-protein signaling modulator 2 in HepG2 and SMMC-7721 cells increased the expression levels of Bax, caspase-3, and E-cadherin, while notably suppressing the cyclin-dependent kinase 4, cyclin-dependent kinase 6, CyclinD1, Snail1, Vimentin, and matrix metallopeptidase 9 expression levels, compared with that in the control groups. In addition, we found that G-protein signaling modulator 2 can affect the expression of key proteins involved in protein kinase B activation. In conclusion, high expression of G-protein signaling modulator 2 was involved in the pathological processes of hepatocellular carcinoma through activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, which may provide an attractive potential diagnostic biomarker and therapeutic target for treatment of hepatocellular carcinoma.

Localization of GPSM2 in the Nucleus of Invasive Breast Cancer Cells Indicates a Poor Prognosis

“…Embryonic development and tumorigenesis have similar molecular mechanisms, and thus, GPSM2 may play an important role in both. A previous study reported that GPSM2 was overexpressed in hepatocellular carcinoma and related to poor prognosis of these patients (11). Another study in pancreatic cancer showed GPSM2 promoted the proliferation and migration ability of CD133+ pancreatic cancer stem cells (12).…”

“…There are several reports of the role of GPSM2 in cancer. For example, in hepatocellular carcinoma (11) and pancreatic cancer (12), overexpression of GPSM2 promotes tumor progression and is related to prognosis. In addition, one study has observed aberrant expression of GPSM2 in breast cancer (13), but, its clinical value needs to be further explored.…”

Knockdown of G‐protein‐signaling modulator 2 promotes metastasis of non‐small‐cell lung cancer by inducing the expression of Snail

“…is higher in hepatocellular carcinoma tissues than in normal liver tissue; in addition, GPSM2 was related to tumor size, infection with hepatitis B virus, and prognosis. 9 However, the role of GPSM2 in NSCLC has yet to be elucidated. Our study is the first to report that the expression levels of GPSM2 protein are consistently downregulated in NSCLC tissue samples and cell lines.…”

“…NC, negative control facilitates tumor metastasis in hepatocellular carcinoma. 9 Another study showed that the downregulation of GPSM2 significantly reduced the ability of cancer to migrate in pancreatic cells. 10 In the present study, we attempted to explore the regulatory effect of GPSM2 in NSCLC metastasis.…”

“…4 In addition, the genetic deletion or mutation of GPSM2 leads to defective brain development and nonsyndromic deafness in mice and humans; these are likely to represent defects in cell polarity. [5][6][7] Recent work identified the aberrant expression of GPSM2 in breast cancer, 8 hepatocellular carcinoma, 9 and pancreatic cancer. 10 However, whether GPSM2 plays a similar role in other tumors remains uncertain.…”