Cellular inhibitor of apoptosis protein 2 promotes the epithelialmesenchymal transition in triple-negative breast cancer cells through activation of the AKT signaling pathway

Su Ji Jo, Pil Gu Park, Hye Ran Cha, Sung Gwe Ahn, Min Jung Kim, Hyemi Kim, JaSeung Koo, Jeong Joon, Jeon Han Park, Seung Myung Dong, Jae Myun Lee

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4 Citations (Scopus)

Abstract

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 epithelialmesenchymal 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.

Original languageEnglish
Pages (from-to)78781-78795
Number of pages15
JournalOncotarget
Volume8
Issue number45
DOIs
Publication statusPublished - 2017 Jan 1

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Triple Negative Breast Neoplasms
Inhibitor of Apoptosis Proteins
Breast Neoplasms
Neoplasm Metastasis
Epithelial-Mesenchymal Transition

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Jo, Su Ji ; Park, Pil Gu ; Cha, Hye Ran ; Ahn, Sung Gwe ; Kim, Min Jung ; Kim, Hyemi ; Koo, JaSeung ; Joon, Jeong ; Park, Jeon Han ; Dong, Seung Myung ; Lee, Jae Myun. / Cellular inhibitor of apoptosis protein 2 promotes the epithelialmesenchymal transition in triple-negative breast cancer cells through activation of the AKT signaling pathway. In: Oncotarget. 2017 ; Vol. 8, No. 45. pp. 78781-78795.
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abstract = "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 epithelialmesenchymal 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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Cellular inhibitor of apoptosis protein 2 promotes the epithelialmesenchymal transition in triple-negative breast cancer cells through activation of the AKT signaling pathway. / Jo, Su Ji; Park, Pil Gu; Cha, Hye Ran; Ahn, Sung Gwe; Kim, Min Jung; Kim, Hyemi; Koo, JaSeung; Joon, Jeong; Park, Jeon Han; Dong, Seung Myung; Lee, Jae Myun.

In: Oncotarget, Vol. 8, No. 45, 01.01.2017, p. 78781-78795.

Research output: Contribution to journalArticle

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AU - Jo, Su Ji

AU - Park, Pil Gu

AU - Cha, Hye Ran

AU - Ahn, Sung Gwe

AU - Kim, Min Jung

AU - Kim, Hyemi

AU - Koo, JaSeung

AU - Joon, Jeong

AU - Park, Jeon Han

AU - Dong, Seung Myung

AU - Lee, Jae Myun

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AB - 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 epithelialmesenchymal 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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