Integrated proteomics identified up-regulated focal adhesion-mediated proteins in human squamous cell carcinoma in an orthotopic murine model

Daniela C Granato; Mariana R Zanetti; Rebeca Kawahara; Sami Yokoo; Romênia R Domingues; Annelize Z Aragão; Michelle Agostini; Marcelo F Carazzolle; Ramon O Vidal; Isadora L Flores; Johanna Korvala; Nilva K Cervigne; Alan R S Silva; Ricardo D Coletta; Edgard Graner; Nicholas E Sherman; Adriana F Paes Leme

doi:10.1371/journal.pone.0098208

Integrated proteomics identified up-regulated focal adhesion-mediated proteins in human squamous cell carcinoma in an orthotopic murine model

PLoS One. 2014 May 23;9(5):e98208. doi: 10.1371/journal.pone.0098208. eCollection 2014.

Authors

Daniela C Granato¹, Mariana R Zanetti¹, Rebeca Kawahara¹, Sami Yokoo¹, Romênia R Domingues¹, Annelize Z Aragão¹, Michelle Agostini², Marcelo F Carazzolle¹, Ramon O Vidal¹, Isadora L Flores³, Johanna Korvala⁴, Nilva K Cervigne⁵, Alan R S Silva⁵, Ricardo D Coletta⁵, Edgard Graner⁵, Nicholas E Sherman⁶, Adriana F Paes Leme¹

Affiliations

¹ Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, Brazil.
² Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, UNICAMP, Piracicaba, Brazil; Faculdade de Odontologia, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil.
³ Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, Brazil; Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, UNICAMP, Piracicaba, Brazil.
⁴ Institute of Dentistry, University of Oulu, Oulu, Finland.
⁵ Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, UNICAMP, Piracicaba, Brazil.
⁶ W. M. Keck Biomedical Mass Spectrometry Lab. University of Virginia, Charlottesville, Virginia, United States of America.

Abstract

Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / pathology
Cell Movement / genetics
Focal Adhesions / genetics
Focal Adhesions / metabolism*
Focal Adhesions / pathology
Gene Expression Regulation, Neoplastic*
Heterografts
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Neoplasm Proteins / biosynthesis*
Neoplasm Proteins / genetics
Neoplasm Transplantation
Neoplasms, Experimental / genetics
Neoplasms, Experimental / metabolism*
Neoplasms, Experimental / pathology
Proteomics / methods
Talin / biosynthesis*
Talin / genetics
Tongue Neoplasms / genetics
Tongue Neoplasms / metabolism*
Tongue Neoplasms / pathology
Up-Regulation / genetics

Substances

Neoplasm Proteins
TLN1 protein, human
Talin

Grants and funding

This work was supported by FAPESP Grants: 2009/54067-3, 2010/19278-0, 2011/22421-2, 2009/53839-2 and 2011/02267-9; CNPq Grants: 470567/2009-0, 470549/2011-4, 301702/2011-0, 470268/2013-1, and 505413/2013-2; and Science without Borders Program Grant MEC/MCTI/CAPES/CNPq/FAPs 109/2012. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.