Activation of p53-p21 is closely associated with the acquisition of resistance to apoptosis caused by β1-integrin silencing in head and neck cancer cells

Title
Activation of p53-p21 is closely associated with the acquisition of resistance to apoptosis caused by β1-integrin silencing in head and neck cancer cells
Authors
김미라장효원남혜윤한명월문소영김효정이희진노종렬김승후김상윤
Keywords
β1-Integrin; p53; EMT; Head and neck cancer cell lines
Issue Date
2012-02
Publisher
Biochemical and biophysical research communications
Citation
VOL 418, NO 2, 260-266
Abstract
The issue of whether aberrant expression of β1-integrin is associated with cancer progression and development of resistance to cytotoxic therapy is of considerable interest. Studies to date have shown that the anchorage-independent survival of cancer is attributed, in part, to epithelial-to-mesenchymal transition (EMT). Here, we have reported a novel alternative mechanism of anchorage-independent survival of cancer cells. Cell lines derived from head and neck cancer patients (AMC-HN-3 and AMC-HN-9) and the well-known EMT cancer cell line, MDA-MB231, were examined. The EMT features of AMC-HN-9 cells were comparable to those of MDA-MB231, whereas AMC-HN-3 cells showed no EMT characteristics. Although the pattern and degree of β1-integrin expression were similar in all three cell lines, sensitivities of the cells to β1-integrin knockdown with small interfering RNA (siRNA) were different. Cancer cells with no EMT features underwent cell death to a more significant extent following β1-integrin silencing than those with EMT. Intriguingly, we observed reactive activation of the p53–p21 pathway after β1-integrin silencing in AMC-HN-9 cells lacking an apparent cell death response. Simultaneous knockdown of wild-type p53 and β1-integrin in this cell line promoted cell death. Our data collectively indicate that β1-integrin-related cell death is closely associated with EMT phenotypes and activation of the p53–p21 pathway is partly involved in the acquisition of resistance to apoptosis induced by β1-integrin silencing. Further clarification of the mechanisms underlying p53 integration with β1-integrin signaling may facilitate the development of novel anti-cancer strategies.
URI
http://pubs.kist.re.kr/handle/201004/43849
ISSN
0006291X
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KIST Publication > Article
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