Open AccessSilencing of ASPP2 promotes the proliferation, migration and invasion of triple-negative breast cancer cells via the PI3K/AKT pathway
Author(s) -
Tianqi Wu,
Hongming Song,
Dan Xie,
Bingkun Zhao,
Hui Xu,
Chenyang Wu,
Kaiyao Hua,
Yunkun Deng,
Changle Ji,
Jiashu Hu,
Lin Fang
Publication year - 2018
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2018.4331
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , gene silencing , cancer research , biology , triple negative breast cancer , apoptosis , downregulation and upregulation , cell growth , cell cycle , small interfering rna , breast cancer , epithelial–mesenchymal transition , transfection , oncogene , kinase , cancer , signal transduction , microbiology and biotechnology , metastasis , cell culture , gene , biochemistry , genetics
Apoptosis-stimulating p53 protein 2 (ASPP2) is an apoptosis inducer that acts via binding with p53 and then enhancing the transcriptional activities toward pro‑apoptosis genes. ASPP2 has recently been reported to serve a major role in p53‑independent pathways. Triple‑negative breast cancer (TNBC) is a type of breast cancer that is more aggressive and highly lethal when p53 is mutated. In the present study, the mRNA level of ASPP2 was found to be suppressed in breast tumors compared with that in adjacent normal breast tissues, and the expression of ASPP2 was also decreased in a series of breast cancer cell lines compared with that in MCF‑10A normal breast cells. Downregulation of ASPP2 by specific small interfering RNA (siRNA) transfection was able to promote cell growth, reduce cell apoptosis, and contribute to cell migration and invasion. Furthermore, downregulation of ASPP2 promoted cell epithelial‑mesenchymal transition (EMT) in MDA‑MB‑231 and HCC‑1937 TNBC cells. Furthermore, it was found that when ASPP2 siRNA was transfected into MDA‑MB‑231 and HCC‑1937 cells, the expression of phosphoinositide‑3‑kinase regulatory subunit 1 (p85α) decreased and phosphorylation of protein kinase B (AKT) increased, which are key molecular regulators in the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. In conclusion, the present data indicated that ASPP2 had a crucial influence on the proliferation and metastasis in TNBC, and that the functional mechanism may be p53‑independent to a great extent. ASPP2 and its link with the PI3K/AKT pathway deserve further investigation and may provide novel insights into therapeutic targets for TNBC.