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

Abstract

Chronic infection of Mycoplasma hyorhinis (M. hyorhinis) has been postulated to be associated with several types of cancer, but its effect on patients' survival and host factors mediating its infection remain unclear. Herein, we demonstrated that M. hyorhinis p37 protein expression in gastric cancer tissues predicts poor survival and associates with metastasis. M. hyorhinis infects mammalian cells and promotes gastric cancer cell invasiveness via its membrane protein p37. Synthesized peptide corresponding to the N-terminus of p37 prevents M. hyorhinis infection. Host Annexin A2 (ANXA2) interacts with the N-terminus of p37. In addition, EGFR forms a complex with p37 and ANXA2, and is required for M. hyorhinis-induced phosphorylation and membrane recruitment of ANXA2. M. hyorhinis infection is inhibited by siRNA-mediated knockdown of ANXA2 or EGFR, but is enhanced by expression of ectopic ANXA2 or EGFR. Downstream of ANXA2 and EGFR, the NF-kB pathway is activated and mediates M. hyorhinis-driven cell migration. In conclusion, our study unveils the effect of M. hyorhinis infection on gastric cancer survival and uncovers the mechanisms by which M. hyorhinis infects mammalian cells and promotes cancer cell migration. Cancer Res; 74(20); 5782-94. Ó2014 AACR.

Mapping of a Mycoplasma-Neutralizing Epitope on the Mycoplasmal p37 Protein

“…hyorhinis to gastric cancer cells, GES-1, and HUVEC cells, indicating that p37 is essential for M . hyorhinis infection [11]. By using CA27, we detected CTCs in the peripheral circulating blood of patients with HCC, which is the first evidence for the presence of mycoplasma-infected CTCs in cancer patients [12].…”

“…Since then, many studies have shown that the mycoplasmal p37 protein increases the invasiveness and metastasis of cancer cells [8–10]. Addition of p37 to gastric carcinoma and prostate cancer cells increases the migration of the cancer cells [8, 10, 11]. The p37 protein also increases gene expression in fibroblasts associated with inflammation and cancer [21].…”

“…Using PD4 antibody targeting the N terminus of p37, the p37 protein was identified in many cancer tissues, including gastric, colon, esophageal, lung, breast, and glioma carcinomas [6]. During mycoplasma infections, the N-terminal region of the p37 protein binds to host annexin A2 and promotes NF-κB-dependent migration of human gastric cancer cells [11]. Another study shows that the C-terminal 20 amino acids of the p37 protein may be involved in p37-induced gene expression in NIH3T3 fibroblasts through toll-like receptor 4 signaling [21].…”

“…Subsequent studies have demonstrated that the mycoplasmal p37 protein results in the proliferation, invasiveness, and metastases of cancer cells [8–10]. A recent study also demonstrated that the p37 protein expression predicts poor survival and metastasis in gastric cancer patients [11]. …”

Induction of anti-EGFR immune response with mimotopes identified from a phage display peptide library by panitumumab

“…Co-IP and GST pull-down were performed as described previously [27]. Briefly, E.coli cell lysates containing GST fusion protein were prepared in lysis buffer (1% Triton X-100, 1 mmol/L PMSF, and 1 mg/mL lysozyme in PBS) followed by sonication.…”