RRC ID 52114
Author Takahara T, Kasamatsu A, Yamatoji M, Iyoda M, Kasama H, Saito T, Takeuchi S, Endo-Sakamoto Y, Shiiba M, Tanzawa H, Uzawa K.
Title SIPA1 promotes invasion and migration in human oral squamous cell carcinoma by ITGB1 and MMP7.
Journal Exp. Cell Res.
Abstract Signal-induced proliferation-associated protein 1 (SIPA1) is known to be a GTPase activating protein. Overexpressed SIPA1 is related to metastatic progression in breast and prostate cancers; however, the relevance of SIPA1 in oral squamous cell carcinoma (OSCC) is still unknown. The aim of this study was to examine SIPA1 expression and its functional mechanisms in OSCC. SIPA1 mRNA and protein expressions were analyzed by quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. The expressions of SIPA1 were up-regulated significantly in vitro and in vivo. Moreover, SIPA1 expression was correlated with regional lymph node metastasis. We next assessed the cellular functions associated with tumoral metastasis using SIPA1 knockdown (shSIPA1) cells and analyzed the downstream molecules of SIPA1, i.e., bromodomain containing protein 4(BRD4), integrin beta1 (ITGB1), and matrix metalloproteinase 7 (MMP7). The shSIPA1 cells showed decreased invasiveness and migratory activities, however cellular adhesion ability was maintained at a high level. In addition, ITGB1 expression was greater in shSIPA1 cells, whereas MMP7 expression was lower than in control cells. This research is the first to establish that SIPA1 promotes cancer metastasis by regulating the ITGB1 and MMP7. Therefore, SIPA1 might be a novel therapeutic target for patients with lymph node metastasis of OSCC.
Volume 352(2)
Pages 357-363
Published 2017-3-15
DOI 10.1016/j.yexcr.2017.02.026
PII S0014-4827(17)30080-0
PMID 28237246
MeSH Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism* Carcinoma, Squamous Cell / pathology Case-Control Studies Cell Line, Tumor Cell Movement* GTPase-Activating Proteins / genetics GTPase-Activating Proteins / metabolism* Humans Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Lymphatic Metastasis Matrix Metalloproteinase 7 / genetics Matrix Metalloproteinase 7 / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism Mouth Neoplasms / genetics Mouth Neoplasms / metabolism* Mouth Neoplasms / pathology Nuclear Proteins / genetics Nuclear Proteins / metabolism*
IF 3.309
Human and Animal Cells HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) Sa3(RCB0980) Ca9-22(RCB1976) SAS(RCB1974) HO-1-u-1(RCB2102)