SIPA1 promotes invasion and migration in human oral squamous cell carcinoma by ITGB1 and MMP7

Journal Article · Wed Mar 15 00:00:00 EDT 2017 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2017.02.026· OSTI ID:22649841

Takahara, Toshikazu ^[1]; Kasamatsu, Atsushi ^[2]; Yamatoji, Masanobu ^[2]; Iyoda, Manabu; Kasama, Hiroki; Saito, Tomoaki ^[3]; Takeuchi, Shin ^[1]; Endo-Sakamoto, Yosuke ^[2]; Shiiba, Masashi ^[4]; Tanzawa, Hideki ^[1]; Uzawa, Katsuhiro ^[1]

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1. Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba (Japan)
2. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba (Japan)
3. Division of Oral Surgery, Chiba Rosai Hospital, Chiba (Japan)
4. Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan)

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. - Highlights: • SIPA1 expression was up-regulated in oral squamous cell carcinoma (OSCC). • SIPA1-positive OSCCs were correlated with regional lymph node metastasis. • SIPA1 controlled BRD4 and influenced transcription of ITGB1and MMP7. • SIPA1 induced cellular invasion and migration and decreased cellular adhesion. • SIPA1 might be a potential biomarker of cancer metastasis for OSCC.

• OSTI ID: 22649841
• Journal Information: Experimental Cell Research, Vol. 352, Issue 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOLOGICAL MARKERS
CARCINOMAS
CHAIN REACTIONS
IN VITRO
IN VIVO
LYMPH
LYMPH NODES
MAMMARY GLANDS
MESSENGER-RNA
METASTASES
MOLECULES
PATIENTS
POLYMERASE CHAIN REACTION
POLYMERASES
POTENTIALS
PROSTATE
TRANSCRIPTION