title: SIPA1 promotes invasion and migration in human oral squamous cell carcinoma by ITGB1 and MMP7.
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.
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Takahara
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan. Electronic address: kasamatsua@faculty.chiba-u.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kasamatsu
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamatoji
authors.affiliation: Division of Oral Surgery, Chiba Rosai Hospital, Chiba, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Iyoda
authors.affiliation: Division of Oral Surgery, Chiba Rosai Hospital, Chiba, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kasama
authors.affiliation: Division of Oral Surgery, Chiba Rosai Hospital, Chiba, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Takeuchi
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Endo-Sakamoto
authors.affiliation: Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiiba
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan. Electronic address: uzawak@faculty.chiba-u.jp.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D020690:GTPase-Activating Proteins; C108257:ITGB1BP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C490403:SIPA1 protein, human; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: Cancer metastasis; Cellular adhesion; Cellular invasion; Oral squamous cell carcinoma (OSCC); Signal-induced proliferation associated protein 1 (SIPA1)