AMIGO2 is involved in the spread of peritoneal metastasis in serous ovarian cancer via promoting adhesion to the peritoneal mesothelial cells.

BACKGROUND: Amphoterin-induced gene and open reading frame 2 (AMIGO2) have been reported to be related to the prognosis of colorectal, gastric, and cervical cancer. However, their association with ovarian cancer remains unclear. This study aimed to elucidate the role of AMIGO2 in ovarian cancer. METHODS: AMIGO2 expression was evaluated using immunohistochemistry in patients with ovarian serous carcinoma. We validated in vitro studies using four serous ovarian cancer cell lines and in vivo studies using a murine model. RESULTS: The AMIGO2-high group had significantly shorter progression-free survival (PFS) than the AMIGO2-low group. The predictive index of the AMIGO2-high group was considerably higher than that of the AMIGO2-low group. The rate of complete cytoreductive surgery was lower in the AMIGO2-high group than in the AMIGO2-low group. Moreover, in vitro studies revealed that four serous ovarian cancer cell lines exhibited AMIGO2 expression and adhesion to mesothelial cells. Adhesion to mesothelial cells was attenuated by AMIGO2 knockdown in SKOV3 and SHIN3 cells. Furthermore, AMIGO2 downregulation in SKOV3 cells significantly suppressed peritoneal dissemination in the murine model. CONCLUSION: These results suggest that high AMIGO2 expression in serous ovarian carcinoma cells contributes to a poor prognosis by promoting peritoneal metastasis through enhanced cell adhesion to mesothelial cells.

AMIGO2 enhances the invasive potential of colorectal cancer by inducing EMT.

In our previous studies, we identified amphoterin-inducible gene and open reading frame 2 (AMIGO2) as a driver gene for liver metastasis and found that AMIGO2 expression in cancer cells worsens the prognosis of patients with colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT) is a trigger for CRC to acquire a malignant phenotype, such as invasive potential, leading to metastasis. However, the role of AMIGO2 expression in the invasive potential of CRC cells remains unclear. Thus, this study aimed to examine AMIGO2 expression and elucidate the mechanisms by which it induces EMT and promotes CRC invasion. Activation of the TGFß/Smad signaling pathway was found involved in AMIGO2-induced EMT, and treatment with the TGFß receptor inhibitor LY2109761 suppressed AMIGO2-induced EMT. Studies using CRC samples showed that AMIGO2 expression was highly upregulated in the invasive front, where AMIGO2 expression was localized to the nucleus and associated with EMT marker expression. These results suggest that the nuclear translocation of AMIGO2 induces EMT to promote CRC invasion by activating the TGFß/Smad signaling pathway. Thus, AMIGO2 is an attractive therapeutic target for inhibiting EMT and metastatic CRC progression.

AMIGO2 expression as a predictor of recurrence in cervical cancer with intermediate risk.

Patients with recurrent cervical cancer have limited treatment options and are often considered to be incurable. Since the expression of amphoterin-induced gene and open reading frame 2 (AMIGO2) in clinical samples is a prognostic factor for colorectal cancer and gastric cancer, the present aimed to elucidate whether it is also a prognostic factor for cervical cancer. Patients with primary cervical cancer who underwent radical hysterectomy or radical trachelectomy at our institution (Faculty of Medicine, Tottori University, Yonago, Japan) between September 2005 and October 2016 were retrospectively collected. Immunohistochemical analysis using a specific antibody against AMIGO2 was performed on 101 tumor samples, and the clinical characteristics, disease-free survival (DFS) and overall survival (OS) of the patients were examined. Patients in the AMIGO2-high group had a shorter 5-year DFS and OS than those in the AMIGO2-low group (P<0.001). Furthermore, AMIGO2 was an independent prognostic factor for DFS in multivariate analysis (P=0.0012). Patients in the AMIGO2-high group exhibited obvious recurrence compared with those in the AMIGO2-low group in the high-(P=0.03) and intermediate-risk groups (P=0.003). Positive lymph node metastasis, and parametrial, stromal and lymph vascular space invasion were significantly more common in AMIGO2-high patients. Taken together, AMIGO2 expression may be a predictive marker of recurrence for cervical cancer. In particular, it may be an indicator to determine the need for postoperative adjuvant therapy in intermediate-risk group patients.