Human Chorionic Gonadotropin β Induces Migration and Invasion via Activating ERK1/2 and MMP-2 in Human Prostate Cancer DU145 Cells

Abstract

We previously demonstrated that human chorionic gonadotropin β (hCGβ) induced migration and invasion in human prostate cancer cells. However, the involved molecular mechanisms are unclear. Here, we established a stable prostate cancer cell line overexpressing hCGβ and tested hCGβ-triggered signaling pathways causing cell migration and invasion. ELISA showed that the hCGβ amount secreted into medium increased with culture time after the hCGβ-transfected cells were incubated for 3, 6, 9, 12 and 24 h. More, hCGβ standards promoted MAPK (ERK1/2) phosphorylation and increased MMP-2 expression and activity in both dose- and time-dependent manners in hCGβ non-transfected cells. In addition, hCGβ promoted ERK1/2 phosphorylation and increased MMP-2 expression and activity significantly in hCGβ transfected DU145 cells. Whereas ERK1/2 blocker PD98059 (25 µM) significantly downregulated phosphorylated ERK1/2 and MMP-2. Particularly, hCGβ promoted cell migration and invasion, yet the PD98059 diminished the hCGβ-induced cell motility under those conditions. These results indicated that hCGβ induced cell motility via promoting ERK1/2 phosphorylation and MMP-2 upregulation in human prostate cancer DU145 cells.

B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts Poor Prognosis of Early-Stage Colorectal Cancer

“…The results of this study are consistent with our proposed theory: by examining the distribution of the β-HCG positive cells, we found that β-HCG protein was mostly located at the invasive front of CRC tumors, the more malignant and aggressive tumor area in which the tumor cells are highly correlated with EMT [26]; while β-HCG had no influence on tumor proliferation, it did promote CRC cell migration and invasion. In addition, Li et al reported that β-HCG promoted migration and invasion in prostate cancer by inhibiting E-cadherin and activating the ERK signaling pathway [27]. Our study also validated β-HCG did decrease the expression of E-cadherin, ZO-1 in membrane and enhance the β-catenin translocation from the membrane to nucleus.…”

Sulforaphane inhibits invasion by phosphorylating ERK1/2 to regulate E-cadherin and CD44v6 in human prostate cancer DU145 cells

“…MMP-2 is one of the most distinctive members of this family and facilitates prostate cancer cell invasion. Previous studies have demonstrated that MMP-2 expression is mediated by ERK1/2 (26,27,47,52). In the present study, we found that SFN significantly decreased MMP-2 expression and activity.…”

“…By contrast, sustained (>15 min stimulation) activation of ERK1/2 exhibited the opposite effects (17,(21)(22)(23)(24)(25). Previous results demonstrated that human chorionic gonadotropin β (hCGβ) promoted cell migration and invasion in human glioblastoma and prostate cancer cells by increasing the expression and activity of MMP-2, resulting from the sustained activation of ERK1/2 (26,27). It was also found that the sustained phosphorylation of ERK1/2 by SFN contributed to the suppression of migration and invasion in human glioblastoma cells (16).…”

Maternal–fetal conflict, genomic imprinting and mammalian vulnerabilities to cancer

“…The b-subunit of chorionic gonadotropin (CGb) is a quintessential product of trophoblast that is expressed by many trophoblastic and non-trophoblastic tumours [14,28] and has been considered a 'definitive cancer biomarker' [16]. Although CGb possesses anti-apoptotic and invasionpromoting activities [29,30], any role in cancer progression must be primate-specific because the duplications that generated a cluster of CGB genes from an ancestral LHB gene are primate-specific [31]. Many similar examples could be given.…”