The role of PTPN13 in invasion and metastasis of lung squamous cell carcinoma.

OBJECTIVES PTPN13 is a new candidate tumor-suppressing gene. To investigate the PTPN13 expression and its potential function in the invasion and metastasis of lung squamous cell carcinoma (LSCC), we performed this study in 91 primary LSCC tissues and the adjacent non-cancerous tissues. METHODS The mRNA expression of PTPN13 and FAK was quantitated by reverse transcription polymerase chain reaction. The protein expression of PTPN13, focal adhesion kinase (FAK) and phosphorylated FAK (P-FAK) was evaluated using immunohistochemical staining and western blotting. The association among PTPN13 expression, FAK expression and the clinicopathological parameters were analyzed. RESULTS PTPN13 expression was down-regulated in LSCC, and was negatively correlated with the cancer grade and stage. FAK mRNA, as well as FAK protein level was elevated in LSCC tissues. P-FAK level, also found increased, had no association with FAK mRNA and FAK protein expression, but had a negative correlation with the PTPN13 expression. P-FAK level had a significant positive correlation with the TNM classification. CONCLUSION The over-expression of FAK and increased FAK phosphorylation plays an important role in the invasion and metastasis of LSCC.

[1]  M. Santoro,et al.  Dysregulated RET signaling in thyroid cancer. , 2008, Endocrinology and metabolism clinics of North America.

[2]  H. Stein,et al.  Oesophageal squamous cell neoplasia in head and neck cancer patients: upregulation of COX-2 during carcinogenesis , 2003, British Journal of Cancer.

[3]  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.

[4]  K. S. Erdmann.  The protein tyrosine phosphatase PTP-Basophil/Basophil-like. Interacting proteins and molecular functions. , 2003, European journal of biochemistry.

[5]  R. Stocco,et al.  A novel protein-tyrosine phosphatase with homology to both the cytoskeletal proteins of the band 4.1 family and junction-associated guanylate kinases. , 1994, The Journal of biological chemistry.

[6]  Ding‐Shinn Chen,et al.  Genetic characterization of fas-associated phosphatase-1 as a putative tumor suppressor gene on chromosome 4q21.3 in hepatocellular carcinoma. , 2006, Clinical cancer research : an official journal of the American Association for Cancer Research.

[7]  J. Minna,et al.  Focus on lung cancer. , 2002, Cancer cell.

[8]  M. Lacroix-Triki,et al.  PTPL1/PTPN13 regulates breast cancer cell aggressiveness through direct inactivation of Src kinase. , 2010, Cancer research.

[9]  C. Mountain,et al.  The international system for staging lung cancer. , 2000, Seminars in surgical oncology.

[10]  G. Viglietto,et al.  The nonreceptor-type tyrosine phosphatase PTPN13 is a tumor suppressor gene in non-small cell lung cancer. , 2012, The American journal of pathology.

[11]  TNM: CLASSIFICATION OF MALIGNANT TUMOURS , 1969 .

[12]  John D Minna,et al.  New molecularly targeted therapies for lung cancer. , 2007, The Journal of clinical investigation.

[13]  J. Yates,et al.  Protein tyrosine phosphatase PTPN13 negatively regulates Her2/ErbB2 malignant signaling , 2008, Oncogene.

[14]  Neil O. Carragher,et al.  The role of focal-adhesion kinase in cancer — a new therapeutic opportunity , 2005, Nature Reviews Cancer.

[15]  P G Drake,et al.  Structural and Evolutionary Relationships among Protein Tyrosine Phosphatase Domains , 2001, Molecular and Cellular Biology.

[16]  A. Gazdar.  Epidermal growth factor receptor inhibition in lung cancer: the evolving role of individualized therapy , 2010, Cancer and Metastasis Reviews.

[17]  G. F. Harris,et al.  The PDZ Binding Motif of Human Papillomavirus Type 16 E6 Induces PTPN13 Loss, Which Allows Anchorage-Independent Growth and Synergizes with Ras for Invasive Growth , 2007, Journal of Virology.

[18]  D. Schlaepfer,et al.  Control of motile and invasive cell phenotypes by focal adhesion kinase. , 2004, Biochimica et biophysica acta.

[19]  K. Alitalo,et al.  VEGFs and receptors involved in angiogenesis versus lymphangiogenesis. , 2009, Current opinion in cell biology.

[20]  Wolfgang Link,et al.  The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. , 2008, Current cancer drug targets.

[21]  Pier Paolo Pandolfi,et al.  Tenets of PTEN Tumor Suppression , 2008, Cell.

[22]  T. Hunter,et al.  Oncogenic kinase signalling , 2001, Nature.

[23]  C. Sawyers,et al.  Targeted cancer therapy , 2004, Nature.

[24]  J. Guan,et al.  Focal adhesion kinase and its signaling pathways in cell migration and angiogenesis. , 2011, Advanced drug delivery reviews.

[25]  G. Carpenter,et al.  ErbB receptors: new insights on mechanisms and biology. , 2006, Trends in cell biology.

[26]  D. Carter.  TNM Classification of Malignant Tumors , 1998 .

[27]  Ji Luo,et al.  The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism , 2006, Nature Reviews Genetics.

[28]  P. Massion,et al.  Expression of focal adhesion kinase in small‐cell lung carcinoma , 2012, Cancer.

[29]  N. Yoo,et al.  Mutational analysis of FLASH and PTPN13 genes in colorectal carcinomas , 2008, Pathology.

[30]  B. Ylstra,et al.  Genomic Profiles Associated with Early Micrometastasis in Lung Cancer: Relevance of 4q Deletion , 2009, Clinical Cancer Research.

[31]  F. Révillion,et al.  Expression of the putative tumor suppressor gene PTPN13/PTPL1 is an independent prognostic marker for overall survival in breast cancer , 2009, International journal of cancer.

[32]  Paolo P. Provenzano,et al.  The role of focal adhesion kinase in tumor initiation and progression , 2009, Cell adhesion & migration.

[33]  Fang Fan,et al.  Cancer Grading Manual , 2007 .

[34]  S. Hanks,et al.  The Signaling and Biological Implications of FAK Overexpression in Cancer , 2006, Clinical Cancer Research.

[35]  Giovanni Parmigiani,et al.  Mutational Analysis of the Tyrosine Phosphatome in Colorectal Cancers , 2004, Science.