Activation of p53-p21 is closely associated with the acquisition of resistance to apoptosis caused by beta 1-integrin silencing in head and neck cancer cells

作者：Kim Mi Ra; Chang Hyo Won; Nam Hae Yun; Han Myung Woul; Moon So Young; Kim Hyo Jung; Lee Hee Jin; Roh Jong Lyel; Kim Seong Who; Kim Sang Yoon^*

来源：Biochemical and Biophysical Research Communications, 2012, 418(2): 260-266.

DOI：10.1016/j.bbrc.2012.01.007

• beta-Integrin
• p53
• EMT
• Head and neck cancer cell lines

The issue of whether aberrant expression of beta 1-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 beta 1-integrin expression were similar in all three cell lines, sensitivities of the cells to beta 1-integrin knockdown with small interfering RNA (siRNA) were different. Cancer cells with no EMT features underwent cell death to a more significant extent following beta 1-integrin silencing than those with EMT. Intriguingly, we observed reactive activation of the p53-p21 pathway after beta 1-integrin silencing in AMC-HN-9 cells lacking an apparent cell death response. Simultaneous knockdown of wild-type p53 and beta 1-integrin in this cell line promoted cell death. Our data collectively indicate that beta 1-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 beta 1-integrin silencing. Further clarification of the mechanisms underlying p53 integration with beta 1-integrin signaling may facilitate the development of novel anti-cancer strategies.

• 出版日期2012-2-10