ILP-2: A New Bane and Therapeutic Target for Human Cancers.

Inhibitor of apoptosis protein-related-like protein-2 (ILP-2), also known as BIRC-8, is a member of the inhibitor of apoptosis protein (IAPs) family, which mainly encodes the negative regulator of apoptosis. It is selectively overexpressed in a variety of human tumors and can help tumor cells evade apoptosis, promote tumor cell growth, increase tumor cell aggressiveness, and appears to be involved in tumor cell resistance to chemotherapeutic drugs. Several studies have shown that downregulation of ILP-2 expression increases apoptosis, inhibits metastasis, reduces cell growth potential, and sensitizes tumor cells to chemotherapeutic drugs. In addition, ILP-2 inhibits apoptosis in a unique manner; it does not directly inhibit the activity of caspases but induces apoptosis by cooperating with other apoptosis-related proteins. Here, we review the current understanding of the various roles of ILP-2 in the apoptotic cascade and explore the use of interfering ILP-2, and the combination of related anti-tumor agents, as a novel strategy for cancer therapy.

Proteomic analysis of inhibitor of apoptosis protein­like protein­2 on breast cancer cell proliferation.

Although inhibitor of apoptosis protein­like protein­2 (ILP­2) is considered to be a novel enhancer of breast cancer proliferation, its underlying mechanism of action remains unknown. Therefore, the present study aimed to investigate the expression profile of ILP­2­related proteins in MCF­7 cells to reveal their effect on promoting breast cancer cell proliferation. The isobaric tags for relative and absolute quantification (iTRAQ) method was used to analyse the expression profile of ILP­2­related proteins in MCF­7 breast cancer cells transfected with small interfering (si)RNA against ILP­2 (siRNA­5 group) and the negative control (NC) siRNA. The analysis of the iTRAQ data was carried out using western blotting and reverse transcription­quantitative PCR. A total of 4,065 proteins were identified in MCF­7 cells, including 241 differentially expressed proteins (DEPs; fold change ≥1.20 or ≤0.83; P<0.05). Among them, 156 proteins were upregulated and 85 were downregulated in the siRNA­5 group compared with in the NC group. The aforementioned DEPs were mainly enriched in 'ECM­receptor interaction'. In addition, the top 10 biological processes related to these proteins were associated with signal transduction, cell proliferation and immune system processes. Furthermore, ILP­2 silencing upregulated N(4)­(ß­N­acetylglucosaminyl)­L­asparaginase, metallothionein­1E and tryptophan 2,3­dioxygenase, whereas ILP­2 overexpression exerted the opposite effect. The results of the present study suggested that ILP­2 could promote breast cancer growth via regulating cell proliferation, signal transduction, immune system processes and other cellular physiological activities.