Interaction between the laminin-derived peptide C16 and beta 1 integrin in breast cancer cells. Mechanisms involved and functional consequences.

• Grant number: 16/20228-4
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): January 01, 2017
• Effective date (End): September 30, 2020
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal researcher: Ruy Gastaldoni Jaeger
• Grantee: Maria Raquel Unterkircher Galheigo
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 19/24179-6 - Study of the laminin 111-derived peptide C16 internalization through endocytic vesicles and its possible exocytosis by breast cancer cells, BE.EP.DR

Abstract

Malignant neoplasms of the female breast are among the most incidents in the Brazilian population, corresponding to 28.1% of the tumors. In this context, the literature clearly shows the important role that the tumor microenvironment takes during the progression and metastasis of cancer. Such a microenvironment is composed of different cell types enmeshed in the extracellular matrix. Laminin-111 is a very important extracellular matrix glycoprotein. This molecule is cleaved by matrix metalloproteinases, giving rise to sequences or peptide fragments with biological activities. Among these bioactive sequences, the C16 peptide presents important effects in tumor biology. We have demonstrated that this peptide influences cancer cells by regulating migration, invasion, invadopodia formation and protease secretion. Furthermore, C16-activity decreases in tumor cells with the expression of beta 1 integrin depleted by RNAi. This prompted us to study in detail the interaction between the peptide C16 and beta1 integrin. Therefore, the goal of this project is to better understand the molecular mechanisms involved in the interaction between the laminin-derived peptide C16 and beta 1 integrin in breast tumor cells. We will also address signaling pathways activated by such interaction, as well as the inherent functional effects.