p37 from Mycoplasma hyorhinis promotes cancer cell invasiveness and metastasis through activation of MMP-2 and followed by phosphorylation of EGFR

Abstract

High Mycoplasma infection in gastric cancer tissues suggests a possible association between Mycoplasma infection and tumorigenesis. By using human gastric cancer cells AGS and mouse melanoma cells B16F10 stably expressing p37, the major immunogen of Mycoplasma hyorhinis, we found that p37 enhanced cell motility, migration, and invasion in vitro. With experimental metastasis model in C57BL/6 mice, p37 adenovirus-infected B16F10 cells formed more metastasis lesions in the lung. Furthermore, p37 promoted the phosphorylation of epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase and the activity of matrix metalloproteinase-2 (MMP-2). Inhibitor of MMPs significantly blocked p37-induced EGFR but has little effect on extracellular signal-regulated kinase phosphorylation, whereas the p37-induced MMP-2 activation was only partially suppressed by inhibitor of MEK1/2 or by inhibitor of EGFR. However, all these inhibitors significantly reduced the p37-induced invasiveness of AGS cells. These results suggest that p37 may stimulate invasion by increasing the activity of MMP-2, thereby inducing EGFR phosphorylation and contributing to tumor metastasis on M. hyorhinis infection. p37 and its regulated molecules could be the potential targets for cancer therapy. [Mol Cancer Ther 2008;7(3):530 -7]

MicroRNA miR-24 Enhances Tumor Invasion and Metastasis by Targeting PTPN9 and PTPRF to Promote EGF Signaling

“…Phosphorylation of EGFR results in activation of downstream MARK, ERK, Akt and JNK signaling pathways leading to DNA synthesis, cell proliferation and cell migration (Schmidt-Ullrich et al, 1997;Sørensen et al, 2006). Thus, phosphorylated EGFR plays important roles in tumor invasion and metastasis (Arora and Simpson, 2008;Gong et al, 2008). Overactivation of EGFR including constant activation and mutations is often associated with cancer development and progression (Lynch et al, 2004;Walker et al, 2009).…”

Mycoplasma Hyorhinis Infection Promotes NF-κB–Dependent Migration of Gastric Cancer Cells

“…p37 shares partial homology to the hemagglutinin protein of influenza A, a sialic acid-binding protein critical for viral entry (18), but p37 has no homology to mammalian proteins. Proinvasive function of p37 has been documented (18,19), but the role of p37 in M. hyorhinis infection and mechanisms underlying M. hyorhinis-and p37-induced malignant phenotypes are unknown. In this study, we demonstrated that M. hyorhinis infection in gastric cancer tissues predicts metastasis and poor survival.…”

Mycoplasma hyorhinis: a potential risk factor in gastric cancer progression

“…Pro-invasive function of p37 has been documented previously by our lab and others' [11,12] , but the role of p37 in M. hyorhinis infection is unclear. In the recently published work on journal "Cancer Research", we found that M. hyorhinis could infect both cancerous and noncancerous cells, while cancer cells were more prone to be infected.…”

“…It was reported that EGFR plays a role in regulating ANXA2 phosphorylation and localization [16] . Moreover, our previous work reported that both M. hyorhinis infection and recombinant p37 treatment could activate EGFR [5,12] , but the role of EGFR in M. hyorhinis infection and M. hyorhinis-induced metastasis are not fully elucidated. We noticed that ANXA2-EGFR interaction was increased and EGFR preferred to interact with phosphorylated ANXA2 in M. hyorhinis-infected cells.…”