Cellular inhibitor of apoptosis protein 2 promotes the epithelial-mesenchymal transition in triple-negative breast cancer cells through activation of the AKT signaling pathway
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Su Ji Jo1,2,*, Pil-Gu Park1,*, Hye-Ran Cha1, Sung Gwe Ahn3, Min Jung Kim1, Hyemi Kim1,2, Ja Seung Koo4, Joon Jeong3, Jeon Han Park1, Seung Myung Dong5,6 and Jae Myun Lee1,2
1Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Republic of Korea
2BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
3Breast Cancer Center, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
4Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
5Research Institute, National Cancer Center, Goyang, Republic of Korea
6IMK Bio-Convergence R&D Center, International Vaccine Institute, Seoul, Republic of Korea
*These authors have contributed equally to this work
Jae Myun Lee, email: email@example.com
Seung Myung Dong, email: firstname.lastname@example.org
Keywords: triple-negative breast cancer, cellular inhibitor of apoptosis protein 2, epithelial-mesenchymal transition, AKT signaling pathway
Received: May 16, 2017 Accepted: July 25, 2017 Published: August 12, 2017
Triple-negative breast cancer (TNBC) represents approximately 10–17% of all breast cancers, and patients with TNBC show a poorer short-term prognosis than patients with other types of breast cancer. TNBCs also have a higher tendency for early distant metastasis and cancer recurrence due to induction of the epithelial-mesenchymal transition (EMT). Several recent reports have suggested that inhibitor of apoptosis (IAP) proteins function as regulators of the EMT. However, the roles of these proteins in TNBC are not clear. Accordingly, we investigated the roles of cIAP2 in TNBC. Among eight IAP genes, only cIAP2 was upregulated in TNBC cells compared with that in other breast cancer subtypes. Analysis of TMAs revealed that expression of cIAP2 was upregulated in TNBCs. In vitro studies showed that cIAP2 was highly expressed in TNBC cells compared with that in other types of breast cancer cells. Furthermore, silencing of cIAP2 in TNBC cells induced mesenchymal-epithelial transition (MET)-like processes and subsequently suppressed the migratory ability and invasion capacity of the cells by regulation of Snail through the AKT signaling pathway. In contrast, ectopic expression of cIAP2 in luminal-type breast cancer cells induced activation of the AKT signaling pathway. These results collectively indicated that cIAP2 regulated the EMT in TNBC via activation of the AKT signaling pathway, contributing to metastasis in TNBC. Our study proposes a novel mechanism through which cIAP2 regulates the EMT involving AKT signaling in TNBC cells. We suggest that cIAP2 may be an attractive candidate molecule for the development of targeted therapeutics in the future.
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