RRC ID |
52114
|
著者 |
Takahara T, Kasamatsu A, Yamatoji M, Iyoda M, Kasama H, Saito T, Takeuchi S, Endo-Sakamoto Y, Shiiba M, Tanzawa H, Uzawa K.
|
タイトル |
SIPA1 promotes invasion and migration in human oral squamous cell carcinoma by ITGB1 and MMP7.
|
ジャーナル |
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.
|
巻・号 |
352(2)
|
ページ |
357-363
|
公開日 |
2017-3-15
|
DOI |
10.1016/j.yexcr.2017.02.026
|
PII |
S0014-4827(17)30080-0
|
PMID |
28237246
|
MeSH |
Adaptor Proteins, Signal Transducing
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 |
3.383
|
引用数 |
13
|
リソース情報 |
ヒト・動物細胞 |
HSC-2(RCB1945)
HSC-3(RCB1975)
HSC-4(RCB1902)
Sa3(RCB0980)
Ca9-22(RCB1976)
SAS(RCB1974)
HO-1-u-1(RCB2102) |