ID1 contributes to cell growth invasion and migration in salivary adenoid cystic carcinoma

Previous studies have reported that inhibitor of DNA binding 1 (ID1) exerts an oncogenic role in a number of tumors. In the present study, the role of ID1 in the growth, invasion and migration of salivary adenoid cystic carcinoma (SACC) cells was investigated. ID1 expression in clinical SACC samples was compared with that in normal salivary tissues using immunohistochemical staining, and the correlation between ID1 expression and clinical pathological characteristics was then determined. Subsequently, ID1 was overexpressed or silenced to investigate the effects of ID1 expression on SACC cell proliferation, invasion and migration. In addition, the gene expression levels of known ID1 target genes, including S100A9, CDKN2A and matrix metalloproteinase 1 (MMP1) was measured using reverse transcription-quantitative polymerase chain reaction to elucidate the potential mechanisms of ID1 in SACC. The results of the present study indicated that the protein expression levels of ID1 were significantly increased in the SACC tissues compared with that in the normal salivary tissues (P<0.001), and a positive correlation between ID1 expression and tumor stage (P=0.001), tumor invasion (P=0.002) and metastasis (P=0.019) in SACC was observed. Knockdown of ID1 in SACC cells significantly inhibited cell growth, invasion and migration (all P<0.01), whereas overexpression of ID1 promoted cell proliferation, invasion and migration (all P<0.01). The gene expression level of MMP1 was significantly reduced following ID1 knockdown in SACC-83 cells when compared with negative controls (P<0.05), whereas S100A9 and CDKN2A expression levels were significantly upregulated (both P<0.05). The results suggest that ID1 may regulate the growth, invasion and migration of SACC cells, and that MMP1, S100A9 and CDKN2A may serve as target genes of ID1 and mediate the effects of ID1 in SACC cells. Therefore, ID1 may present a potential target gene for the treatment of patients with SACC to inhibit cancer cell growth and metastasis.

[1]  J. Xie,et al.  FZD2 inhibits the cell growth and migration of salivary adenoid cystic carcinomas. , 2016, Oncology reports.

[2]  Yangxing Zhao,et al.  RASSF1A Promoter Hypermethylation Is a Strong Biomarker of Poor Survival in Patients with Salivary Adenoid Cystic Carcinoma in a Chinese Population , 2014, PloS one.

[3]  J. Xie,et al.  NOTCH1 signaling contributes to cell growth, anti-apoptosis and metastasis in salivary adenoid cystic carcinoma , 2014, Oncotarget.

[4]  Qihong Huang,et al.  ID1 Promotes Breast Cancer Metastasis by S100A9 Regulation , 2014, Molecular Cancer Research.

[5]  S. Zhang,et al.  Expression and Clinical Significance of Id-1 ,-3 in Cervical Intraepithelial Neoplasia and Cervical Sqamous Cell Cancer , 2014 .

[6]  M. Komada,et al.  ERK-Dependent Downregulation of Skp2 Reduces Myc Activity with HGF, Leading to Inhibition of Cell Proliferation through a Decrease in Id1 Expression , 2013, Molecular Cancer Research.

[7]  E. Langenfeld,et al.  Small molecule antagonist of the bone morphogenetic protein type I receptors suppresses growth and expression of Id1 and Id3 in lung cancer cells expressing Oct4 or nestin , 2013, Molecular Cancer.

[8]  Lili Sun,et al.  [Expression of Id1 and Id3 in endometrial carcinoma and their roles in regulating biological behaviors of endometrial carcinoma cells in vitro]. , 2013, Nan fang yi ke da xue xue bao = Journal of Southern Medical University.

[9]  R. Ferris,et al.  Molecular biology of adenoid cystic carcinoma , 2012, Head & neck.

[10]  K. Shirasuna,et al.  The T-box transcription factor Brachyury regulates epithelial–mesenchymal transition in association with cancer stem-like cells in adenoid cystic carcinoma cells , 2012, BMC Cancer.

[11]  R. Weber,et al.  Developmental transcription factor EN1—a novel biomarker in human salivary gland adenoid cystic carcinoma * , 2012, Cancer.

[12]  Guang Yang,et al.  Downregulation of Id1 by small interfering RNA in gastric cancer inhibits cell growth via the Akt pathway , 2012, Molecular medicine reports.

[13]  Yun-Ju Chen,et al.  Id1 promotes lung cancer cell proliferation and tumor growth through Akt-related pathway. , 2011, Cancer letters.

[14]  G. Bepler,et al.  ID1 Facilitates the Growth and Metastasis of Non-Small Cell Lung Cancer in Response to Nicotinic Acetylcholine Receptor and Epidermal Growth Factor Receptor Signaling , 2011, Molecular and Cellular Biology.

[15]  R. Valcavi,et al.  Inhibitor of DNA binding-1 induces mesenchymal features and promotes invasiveness in thyroid tumour cells. , 2011, European journal of cancer.

[16]  A. Ho,et al.  Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review. , 2011, The Lancet. Oncology.

[17]  M. Tschan,et al.  The stem cell gene "inhibitor of differentiation 1" (ID1) is frequently expressed in non-small cell lung cancer. , 2011, Lung cancer.

[18]  J. Tao,et al.  Downregulation of Id1 by small interfering RNA in prostate cancer PC3 cells in vivo and in vitro , 2011, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[19]  Yin-cheng Zhang,et al.  erbB2 gene silencing and its effect on PTEN in SACC-83 salivary adenoid cystic carcinoma cells. , 2010, Oncology reports.

[20]  R. Benezra,et al.  Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth. , 2010, Cancer research.

[21]  Wei Guo,et al.  Expression and importance of inhibitor of DNA binding helix-loop-helix protein in salivary adenoid cystic carcinoma. , 2010, The British journal of oral & maxillofacial surgery.

[22]  J. Herman,et al.  Id1 overexpression is independent of repression and epigenetic silencing of tumor suppressor genes in melanoma , 2010, Epigenetics.

[23]  Y. Yap,et al.  Id1, inhibitor of differentiation, is a key protein mediating anti-tumor responses of gamma-tocotrienol in breast cancer cells. , 2010, Cancer letters.

[24]  H. Hamakawa,et al.  Overexpression of Id-1 is associated with tumor angiogenesis and poor clinical outcome in oral squamous cell carcinoma. , 2010, Oral oncology.

[25]  Xiaohui Xu,et al.  Inhibitor of DNA Binding-1 Overexpression in Prostate Cancer: Relevance to Tumor Differentiation , 2009, Pathology & Oncology Research.

[26]  C. Brantsing,et al.  Evaluation of p16 and Id1 status and endogenous reference genes in human chondrosarcoma by real-time PCR. , 2005, International journal of oncology.

[27]  Y. Wong,et al.  Overexpression of Id-1 in prostate cancer cells promotes angiogenesis through the activation of vascular endothelial growth factor (VEGF). , 2005, Carcinogenesis.

[28]  E. Patsouris,et al.  Adenoid cystic carcinoma of the head and neck. Clinicopathological analysis of 23 patients and review of the literature. , 2005, Oral oncology.

[29]  T. Tong,et al.  Regulation of Cellular Senescence and p16INK4a Expression by Id1 and E47 Proteins in Human Diploid Fibroblast* , 2004, Journal of Biological Chemistry.

[30]  J. Norton,et al.  Id Proteins Negatively Regulate Basic Helix-Loop-Helix Transcription Factor Function by Disrupting Subnuclear Compartmentalization* , 2003, Journal of Biological Chemistry.

[31]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[32]  Chen Ya Effect of DNA-binding protein inhibitor Id1 on the proliferation of osteosarcoma cells , 2014 .

[33]  Lin Zhang,et al.  Signal Transduction ID 1 Promotes Breast Cancer Metastasis by S 100 A 9 Regulation , 2014 .

[34]  W. Ping Expression and clinical significance of ID1 in gastric cancer , 2013 .

[35]  Jin Ya Expression of Id1 and its correlation with tumor angiogenesis in salivary adenoid cystic carcinoma , 2011 .