c-Myc transactivates GP73 and promotes metastasis of hepatocellular carcinoma cells through GP73-mediated MMP-7 trafficking in a mildly hypoxic microenvironment

Abstract

Golgi phosphoprotein 73 (GP73), encoded by GOLM1, is a highly expressed factor in hepatocellular carcinoma (HCC) cells and has been regarded for several years as a remarkable serum biomarker for the diagnosis of HCC. Recently, it was found that upregulation of GP73 promotes cancer metastasis, but the mechanism is complex, and it is even unclear how the gene is transactivated in HCC cells. In this study, it was discovered that c-Myc transactivated GP73 in a mildly hypoxic microenvironment and that the activation of c-Myc upregulated the expression of matrix metalloproteinase-7 (MMP-7). Moreover, it is shown that GP73 interacted with intracellular MMP-7 in the region of the cytoplasmic domain and facilitated the trafficking and secretion of MMP-7, resulting in cell metastasis. This study indicates that GP73 is transactivated by c-Myc and serves as a transporter in the trafficking of intracellular MMP-7 in HCC cells. These findings suggest that GP73 is a potential target for combating metastatic HCC.

Recent advances of GOLM1 in hepatocellular carcinoma

“…Among them, GOLM1 (also known as GP73 or GOLPH2) is the most anticipated tumor biomarker. A growing number of studies have shown that the abnormal expression of GOLM1 is associated with HCC and may become a new target for the prevention, monitoring and treatment of HCC [4][5][6][7]. In this review, we discuss the recent advances of GOLM1 in HCC and present an overall view of future research.…”

Regulating Tumor N6‐Methyladenosine Methylation Landscape using Hypoxia‐Modulating OsSx Nanoparticles

“…[ 40,43 ] Hypoxia can significantly reduce the effectiveness and cause resistance of radiotherapy and chemotherapy. [ 10 ] Possible reason is that hypoxia can increase expression of pre‐survival genes including c‐myc, [ 44 ] AMPK, [ 45 ] GLUT1, [ 46 ] and BNIP3. [ 47 ] Hypoxia can also promote tumor angiogenesis, [ 48 ] EMT, [ 49 ] invasion, [ 50 ] metastasis, [ 9 ] glycolysis, [ 51 ] metabolism, [ 52 ] and survival by regulate hundreds of genes involved in these processes.…”

Vesicle transporter GOLT1B mediates the cell membrane localization of DVL2 and PD-L2 and promotes colorectal cancer metastasis

“…Golgi phosphorylated protein 3 (GOLPH3) promotes the development of CRC and induce resistance to 5-FU by mediating the mTOR pathway [ 18 – 20 ]. Golgi membrane protein 1 (GOLM1) expression is correlated with early recurrence, metastasis, and poor survival of HCC patients [ 21 , 22 ]. Golgi vesicle transporter 1A (GOLT1A) has been shown to regulate tamoxifen sensitivity in breast cancer and promote cell proliferation in lung cancer [ 23 , 24 ].…”