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Association of overexpressed karyopherin alpha 2 with poor survival and its contribution to interleukin‐1β‐induced matrix metalloproteinase expression in oral cancer
Author(s) -
Wang ChunI,
Yu ChiaJung,
Huang Yenlin,
Yi JuiShan,
Cheng HsingWen,
Kao HuangKai,
Lao William WeiKai,
Chang KaiPing
Publication year - 2018
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.25145
Subject(s) - karyopherin , immunohistochemistry , cancer research , gene knockdown , biology , metastasis , matrix metalloproteinase , microbiology and biotechnology , pathology , cancer , medicine , immunology , cell nucleus , apoptosis , gene , biochemistry , nuclear transport
Background The purpose of this study was to elucidate the clinicopathological associations and molecular mechanisms of karyopherin alpha 2 (KPNA2) in oral cavity squamous cell carcinoma (SCC) progression. Methods The KPNA2 expressions were analyzed by immunohistochemistry and enzyme‐linked immunosorbent assay in 209 tissues and 181 saliva samples, respectively. The functions of KPNA2 in migration and invasion were examined in KPNA2‐knowdown cells. The matrix metalloproteinase (MMP) levels were determined by real‐time quantitative polymerase chain reaction (qPCR). The subcellular fraction was used to obtain the nuclear distribution of nuclear factor‐kappa B (NF‐κB). Results The KPNA2 overexpression was associated with extranodal extension ( P < .05) and poor disease‐specific survival in patients with oral cavity SCC ( P < .05). The salivary KPNA2 levels were elevated in patients with oral cavity SCC ( P < .05). The KPNA2 knockdown reduced cell migration and invasion. This knockdown also suppressed the interleukin (IL)‐1β‐induced nuclear import of NF‐κB and MMP (MMP‐1, MMP‐3, and MMP‐9) transcription. Conclusion The KPNA2 overexpression is an independent biomarker for poor prognosis of oral cavity SCC and is required for MMP‐mediated metastasis.