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.
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.
authors.affiliation: Department of Otolaryngology, Bundang Jesaeng General Hospital, Daejin Medical Center, Seongnam, Republic of Korea.
authors.forename: Mi Ra
authors.initials: MR
authors.lastname: Kim
authors.forename: Hyo Won
authors.initials: HW
authors.lastname: Chang
authors.forename: Hae Yun
authors.initials: HY
authors.lastname: Nam
authors.forename: Myung Woul
authors.initials: MW
authors.lastname: Han
authors.forename: So Young
authors.initials: SY
authors.lastname: Moon
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jong-Lyel
authors.initials: JL
authors.lastname: Roh
authors.forename: Seong Who
authors.initials: SW
authors.lastname: Kim
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D019012:Integrin beta1; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53