Dr. Ester Martín Villar

Dr. Esther Grueso Hierro
Dr. Susana Álvarez Losada
Dr. Lucía Montero Montero

Rocío Jarcovsky González
Santiago Garcés Fernández
Sara Temprano Carazo

Rocío Jarcovsky González

Santiago Garcés

• To investigate the molecular mechanisms by which promoting agents trigger malignant transformation/progression in epidermoid carcinomas of the skin or oral cavity
• To establish diagnostic/prognostic markers of epidermoid carcinomas and investigate their molecular mechanisms to help define more personalized therapies
• To elucidate the mechanisms of early invasion employed by tumor cells
• To investigate new interactions between the different cellular compartments present in the tumor microenvironment

Squamous cell carcinoma or SCC develops mainly from stratified epithelia such as the epidermis, or the mucous membranes of the oral cavity and upper airways. It is one of the most frequent malignant neoplasms in the world. The cause of these tumor lesions and their progression over time are still unknown to us. Its origin appears to be multifactorial, i.e. resulting from the cumulative effect of various environmental factors (e.g. exposure to carcinogens such as ultraviolet light, tobacco and alcohol) in combination with genetic predisposition. These factors induce the transformation of epithelial cells, the ultimate consequence of which is the development of cancer. Among the main causes of death in SCC patients are the reappearance of lesions after their removal, the formation of new secondary tumors and metastases. Late diagnosis of the disease is also one of the main aggravating factors.

The general objective of our research is to extend our basic knowledge of the biology of carcinomas, delving into the molecular mechanisms by which certain molecules may be actively involved in the biogenesis and progression of epidermoid carcinomas. Our interest is also to understand and define the interactions that take place between the different cellular compartments present in the tumor microenvironment. For this purpose, we employ new animal and cellular models in combination with different microscopy, cellular and molecular biology strategies. The ultimate goal of our research is to help define the usefulness of certain biomarkers as indicators of tumor aggressiveness in the hope of helping to establish a better prognosis of the disease at earlier stages, or to define new therapeutic strategies.

Lucía Montero-Montero, Jaime Renart, Andrés Ramírez, Carmen Ramos, Mariam Shamhood, Rocío Jarcovsky, Miguel Quintanilla, Ester Martín-Villar. Interplay between Podoplanin, CD44s and CD44v in Squamous Carcinoma Cells. Cells. 2020 Sep 29;9(10):2200. doi: 10.3390/cells9102200.

Moncho-Amor V, Pintado-Berninches L, Ibañez de Cáceres I, Martín-Villar E,Quintanilla M, Chakravarty P, Cortes-Sempere M, Fernández-Varas B, Rodriguez-Antolín C, de Castro J, Sastre L, Perona R. Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer. Int J Mol Sci. 2019 Apr 25;20(8). pii: E2036. doi:10.3390/ijms20082036. PubMed PMID: 31027181; PubMedCentral PMCID: PMC6514584.

Quintanilla M, Montero-Montero L, Renart J, Martín-Villar E. Podoplanin in Inflammation and Cancer. Int J Mol Sci. 2019 Feb 6;20(3). pii: E707. doi:10.3390/ijms20030707. Review. PubMed PMID: 30736372; PubMed Central PMCID:PMC6386838.

da Silva IL, Montero-Montero L, Martín-Villar E, Martin-Pérez J, Sainz B,Renart J, Toscano Simões R, Soares Veloso É, Salviano Teixeira C, de Oliveira MC,Ferreira E, Quintanilla M. Reduced expression of the murine HLA-G homolog Qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells. Sci Rep. 2017 Jul 24;7(1):6276. doi:10.1038/s41598-017-06528-x. PubMed PMID: 28740236; PubMed Central PMCID:PMC5524840.

Luengo-Gil G, Calvo MI, Martín-Villar E, Águila S, Bohdan N, Antón AI, Espín S, Ayala de la Peña F, Vicente V, Corral J, Quintanilla M, Martínez-Martínez I.Antithrombin controls tumor migration, invasion and angiogenesis by inhibition of enteropeptidase. Sci Rep. 2016 Jun 8;6:27544. doi: 10.1038/srep27544. PubMed PMID: 27270881; PubMed Central PMCID: PMC4897635.

Carrasco-Ramirez P, Greening DW, Andres G, Gopal SK, Martin-Villar E, Renart J, Simpson RJ, Quintanilla M. Podoplanin is a component of extracellular vesicles that reprograms cell-derived exosomal proteins and modulates lymphatic vessel formation. Oncotarget. 2016 Mar 29;7(13):16070-89. doi: 10.18632/oncotarget.7445. PubMed PMID: 26893367; PubMed Central PMCID: PMC4941298.

Renart J, Carrasco-Ramírez P, Fernández-Muñoz B, Martín-Villar E, Montero L, Yurrita MM, Quintanilla M. New insights into the role of podoplanin in epithelial-mesenchymal transition. Int Rev Cell Mol Biol. 2015;317:185-239. doi:10.1016/bs.ircmb.2015.01.009. Epub 2015 Mar 5. Review. PubMed PMID: 26008786.

Pérez-Gómez E, Andradas C, Blasco-Benito S, Caffarel MM, García-Taboada E, Villa-Morales M, Moreno E, Hamann S, Martín-Villar E, Flores JM, Wenners A, Alkatout I, Klapper W, Röcken C, Bronsert P, Stickeler E, Staebler A, Bauer M, Arnold N, Soriano J, Pérez-Martínez M, Megías D, Moreno-Bueno G, Ortega-Gutiérrez S, Artola M, Vázquez-Villa H, Quintanilla M, Fernández-Piqueras J, Canela EI,McCormick PJ, Guzmán M, Sánchez C. Role of cannabinoid receptor CB2 in HER2 pro oncogenic signaling in breast cancer. J Natl Cancer Inst. 2015 Apr 8;107(6):djv077. doi: 10.1093/jnci/djv077. Print 2015 Jun. PubMed PMID: 25855725.

del Castillo G, Sánchez-Blanco E, Martín-Villar E, Valbuena-Diez AC, Langa C, Pérez-Gómez E, Renart J, Bernabéu C, Quintanilla M. Soluble endoglin antagonizes Met signaling in spindle carcinoma cells. Carcinogenesis. 2015 Feb;36(2):212-22. doi: 10.1093/carcin/bgu240. Epub 2014 Dec 10. PubMed PMID: 25503931.

Martín-Villar E, Borda-d’Agua B, Carrasco-Ramirez P, Renart J, Parsons M, Quintanilla M, Jones GE. Podoplanin mediates ECM degradation by squamous carcinoma cells through control of invadopodia stability. Oncogene. 2015 Aug 20;34(34):4531-44. doi: 10.1038/onc.2014.388. Epub 2014 Dec 8. PubMed PMID:25486435; PubMed Central PMCID: PMC4430312.

Griera M, Martin-Villar E, Banon-Rodriguez I, Blundell MP, Jones GE, Anton IM, Thrasher AJ, Rodriguez-Puyol M, Calle Y. Integrin linked kinase (ILK)regulates podosome maturation and stability in dendritic cells. Int J Biochem Cell Biol. 2014 May;50:47-54. doi: 10.1016/j.biocel.2014.01.021. Epub 2014 Feb 6.PubMed PMID: 24508783; PubMed Central PMCID: PMC3998073.

Yurrita MM, Fernández-Muñoz B, Del Castillo G, Martín-Villar E, Renart J, Quintanilla M. Podoplanin is a substrate of presenilin-1/γ-secretase. Int J Biochem Cell Biol. 2014 Jan;46:68-75. doi: 10.1016/j.biocel.2013.11.016. Epub 2013 Nov 22. PubMed PMID: 24275092.

Pérez-Gómez E, Jerkic M, Prieto M, Del Castillo G, Martín-Villar E, Letarte M, Bernabeu C, Pérez-Barriocanal F, Quintanilla M, López-Novoa JM. Impaired wound repair in adult endoglin heterozygous mice associated with lower NO bioavailability. J Invest Dermatol. 2014 Jan;134(1):247-255. doi:10.1038/jid.2013.263. Epub 2013 Jun 13. PubMed PMID: 23765132.

Fernández-Muñoz B, Yurrita MM, Martín-Villar E, Carrasco-Ramírez P, Megías D, Renart J, Quintanilla M. The transmembrane domain of podoplanin is required for its association with lipid rafts and the induction of epithelial-mesenchymal transition. Int J Biochem Cell Biol. 2011 Jun;43(6):886-96. doi:10.1016/j.biocel.2011.02.010. Epub 2011 Mar 3. PubMed PMID: 21376833.

Martín-Villar E, Fernández-Muñoz B, Parsons M, Yurrita MM, Megías D,Pérez-Gómez E, Jones GE, Quintanilla M. Podoplanin associates with CD44 to promote directional cell migration. Mol Biol Cell. 2010 Dec;21(24):4387-99. doi:10.1091/mbc.E10-06-0489. Epub 2010 Oct 20. PubMed PMID: 20962267; PubMed Central PMCID: PMC3002391.

Larriba MJ, Martín-Villar E, García JM, Pereira F, Peña C, de Herreros AG, Bonilla F, Muñoz A. Snail2 cooperates with Snail1 in the repression of vitamin D receptor in colon cancer. Carcinogenesis. 2009 Aug;30(8):1459-68. doi:10.1093/carcin/bgp140. Epub 2009 Jun 5. PubMed PMID: 19502595.

Martín-Villar E, Yurrita MM, Fernández-Muñoz B, Quintanilla M, Renart J.Regulation of podoplanin/PA2.26 antigen expression in tumour cells. Involvement of calpain-mediated proteolysis. Int J Biochem Cell Biol. 2009 Jun;41(6):1421-9. doi: 10.1016/j.biocel.2008.12.010. Epub 2008 Dec 25. PubMed PMID: 19146981.

Martín-Villar E, Megías D, Castel S, Yurrita MM, Vilaró S, Quintanilla M. Podoplanin binds ERM proteins to activate RhoA and promote epithelial-mesenchymal transition. J Cell Sci. 2006 Nov 1;119(Pt 21):4541-53. Epub 2006 Oct 17. PubMed PMID: 17046996.

Martín-Villar E, Scholl FG, Gamallo C, Yurrita MM, Muñoz-Guerra M, Cruces J, Quintanilla M. Characterization of human PA2.26 antigen (T1alpha-2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas. Int J Cancer. 2005 Mar 1;113(6):899-910. PubMed PMID: 15515019.

Muñoz-Guerra MF, Marazuela EG, Martín-Villar E, Quintanilla M, Gamallo C. Prognostic significance of intratumoral lymphangiogenesis in squamous cell carcinoma of the oral cavity. Cancer. 2004 Feb 1;100(3):553-60. PubMed PMID: 14745872.