Proteases e Biologia do Câncer

Biologia Celular e Molecular de Cancer

Linhas gerais/General Information
O objetivo principal do nosso laboratório é entender os mecanismos genéticos e celulares envolvidos na transformação maligna da cavidade oral e do colo de útero, com ênfase no estudo de serino proteases e seus inibidores.

The aim of Dr. Sales’ Laboratory is to understand the cellular and genetic mechanisms involved in cancer initiation in the mouth and uterine cervix, with special focus on serine protease and its inhibitors.

Linhas de pesquisa/Research Aims

A alta incidência do carcinoma epidermóide, seu caráter infiltrativo, possibilidade de causar metástases e baixa sobrevida justificam o investimento na compreensão das vias proteolíticas envolvidas nesse processo neoplásico. As serino proteases e seus inibidores, cruciais para a manutenção dos tecidos saudáveis, atuam como pivôs da destruição tecidual em muitas patologias, que incluem neoplasias malignas. Neste sentido, as serino proteases mostram-se úteis como marcadores de prognóstico em diferentes tipos de cânceres, onde a atividade proteolítica destas enzimas encontra-se desbalanceada. Através da investigação translacional com a utilização de modelos animais (camundongos transgênicos), biologia celular e tecidual, buscamos informações que fundamentem o desenho de intervenções clínicas apropriadas e o desenvolvimento de terapias resolutivas.

The high incidence, low survival rates, infiltrative and metastatic potential of oral and cervical cancers (in particular squamous cell carcinoma) prompted us to better understand the involved proteolytic pathways in these devastating diseases. Although serine proteases and their inhibitors are essential to normal physiology, they can also be involved in tissue damage in several pathological processes, including cancer. Indeed, serine proteases are good candidates for the development of new prognostic markers for several types of cancer, where they have disregulated activity. Our studies focus on a translational perspective starting from pre-clinical information that might ultimately contribute to targeted therapies. For this, we use a variety of tools, including:

1- Transgenic mouse models,

2- Cellular biology,

3- Molecular biology

4- Tissue biology.

 

Alunos de Iniciação Científica (ordem alfabética):

Larissa Silva Coimbra (email: larissa.silva.coimbra@usp.br)

Manuella Cazelato Pires (email: manu_cpires@hotmail.com)

Marina Ferreira Cândido (email: mahfcandido@gmail.com)

Naira Lopes Bibó (email: naira.bibo@usp.br)

Alunos de Mestrado (ordem alfabética):

Bruno Belmonte Martinelli Gomes (email: brunobmgomes@hotmail.com)

Gabriel Viliod Vieira (email: gabrielviliod@gmail.com)

Márcio Hideki Kodama (email: marciohkodama@gmail.com)

Rodrigo Alberto Alves da Silva (email: rodrigo.rodris@hotmail.com)

Pós-doutoranda:

Elaine Zayas Marcelino da Silva (email: ezm_mada@hotmail.com)

Estagiária:

Márcia Gaião Alves (email: alvesg.marcia@gmail.com)

Sugestão de Leitura/Relevant Publications

1. http://www.nidcr.nih.gov/research/ResearchResults/InterviewsOHR/Netherto….

2. SALES, K U ; FRIIS, S ; KONKEL, J E ; GODIKSEN, S ; HATAKEYAMA, M ; HANSEN, K K ; ROGATTO, S R ; Szabo, R ; VOGEL, L K ; CHEN, W ; GUTKIND, J S ; BUGGE, T H . Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant progression and potentiation of ras-mediated squamous cell carcinogenesis. Oncogene (Basingstoke), v. 1, p. 00, 2014.

3. PETERS, D. E. ; SZABO, R. ; FRIIS, S. ; SHYLO, N. A. ; SALES, K. U. ; HOLMBECK, K. ; BUGGE, T. H. . The Membrane-Anchored Serine Protease Prostasin (CAP1/PRSS8) Supports Epidermal Development and Postnatal Homeostasis Independent of its Enzymatic Activity. The Journal of Biological Chemistry (Print), v. n/a, p. n/a, 2014.

4. FRIIS, S. ; SALES, K. U. ; SCHAFER, J. M. ; VOGEL, L. K. ; KATAOKA, H. ; BUGGE, T. H. . The protease inhibitor HAI-2, but not HAI-1, regulates matriptase activation and shedding through prostasin. The Journal of Biological Chemistry (Print), v. epub, p. 0/0, 2014.

5. SALES, K U ; FRIIS, S ; ABUSLEME, L ; MOUTSOPOULOS, N M ; BUGGE, T H . Matriptase promotes inflammatory cell accumulation and progression of established epidermal tumors. Oncogene (Basingstoke), v. 00, p. Epub, 2014.

6. FRIIS, S. ; UZZUN SALES, K. ; GODIKSEN, S. ; PETERS, D. E. ; LIN, C.-Y. ; VOGEL, L. K. ; BUGGE, T. H. . A Matriptase-Prostasin Reciprocal Zymogen Activation Complex with Unique Features: PROSTASIN AS A NON-ENZYMATIC CO-FACTOR FOR MATRIPTASE ACTIVATION. The Journal of Biological Chemistry (Print), v. 288, p. 19028-19039, 2013.

7. GODIKSEN, SINE ; SOENDERGAARD, CHRISTOFFER ; FRIIS, STINE ; JENSEN, JAN K. ; BORNHOLDT, JETTE ; Sales, Katiuchia Uzzun ; HUANG, MINGDONG ; BUGGE, THOMAS H. ; VOGEL, LOTTE K. . Detection of Active Matriptase Using a Biotinylated Chloromethyl Ketone Peptide. Plos One, v. 8, p. e77146, 2013.

8. SALES, KU ; GIUDICE, FS ; CASTILHO, RM ; Salles, FT ; SQUARIZE, CH ; ABRAHAO, AC ; PINTO, DS . Cyclin D1-induced proliferation is independent of beta-catenin in Head and Neck Cancer. Oral Diseases, v. 20, p. n/a-n/a, 2013.

9. Szabo, Roman ; Uzzun Sales, Katiuchia ; KOSA, PETER ; SHYLO, NATALIA A. ; GODIKSEN, SINE ; HANSEN, KARINA K. ; FRIIS, STINE ; GUTKIND, J. SILVIO ; VOGEL, LOTTE K. ; HUMMLER, EDITH ; CAMERER, ERIC ; BUGGE, THOMAS H. ; SCOTT, HAMISH S. . Reduced Prostasin (CAP1/PRSS8) Activity Eliminates HAI-1 and HAI-2 Deficiency Associated Developmental Defects by Preventing Matriptase Activation. PLOS Genetics (Online), v. 8, p. e1002937, 2012.

10. Sales, Katiuchia Uzzun ; HOBSON, JOHN P. ; WAGENAAR-MILLER, REBECCA ; Szabo, Roman ; RASMUSSEN, AMBER L. ; BEY, ALEXANDRA ; SHAH, MAHAM F. ; MOLINOLO, ALFREDO A. ; BUGGE, THOMAS H. ; BOGYO, MATTHEW . Expression and Genetic Loss of Function Analysis of the HAT/DESC Cluster Proteases TMPRSS11A and HAT. Plos One, v. 6, p. e23261, 2011.

11.  MASEDUNSKAS, A. ; SRAMKOVA, M. ; PARENTE, L. ; SALES, K. U. ; AMORNPHIMOLTHAM, P. ; BUGGE, T. H. ; WEIGERT, R. . Role for the actomyosin complex in regulated exocytosis revealed by intravital microscopy. Proceedings of the National Academy of Sciences of the United States of America (Online), v. 108, p. 13552-13557, 2011..

12. SALES, K. U. ; Masedunskas, Andrius ; Bey, Alexandra L ; Rasmussen, Amber L ; Weigert, Roberto ; List, Karin ; Szabo, Roman ; Overbeek, Paul A ; Bugge, Thomas H . Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome. Nature Genetics, v. 42, p. 676-683, 2010.