Hematogenous tumor metastasis in colorectal cancer cells: influence of tyrosine phosphatases and 3-bromopyruvate

Author(s)

Alessandra Valéria de Sousa Faria

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2020-09-16

Examining board members

Carmen Veríssima Ferreira; Marcelo Bispo de Jesus; Ana Carolina Santos de Souza; Edgar Julia Paredes Gamero; Fábio Rogério de Moraes

• Advisor: Carmen Veríssima Ferreira

Abstract

Despite the widespread investigation about drug resistance in cancer, this is one of the major risks associated to treatment failure, especially regarding metastasis process. Over the last two decades, our research group has been investigating the contribution of signal transduction to cancer biology. Our main focus is to evaluate molecular targets to overcome cancer cells aggressiveness and chemoresistance. The Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) is the principal target of our studies, and we have pointed out the relevance of LMWPTP for chemoresistance and metastasis in several tumor models: chronic myeloid leukemia, prostate cancer and including in colorectal cancer. In solid tumors, we also described that LMWPTP overexpression in patient samples is associated to cancer malignancy and patient survival. LMWPTP emerged as a poor prognostic and development stage biomarker, as a correlation between proportional expression of LMWPTP to higher degree of dysplasia and liver metastasis was observed for colorectal cancer. However, a further elucidation of the role of LMWPTP signaling in cancerous processes requires further attention in order to develop secondary lines of treatment. On aspect of hematogenous dissemination, as part of metastasis process, tumor cells escape for blood circulation and, as strategy for survival, interact with platelets. On this context, using colorectal cancer cell models and LMWPTP inhibitor (3-bromopyruvate), it was possible to demonstrate: 1) 3-brompyruvate targets protein tyrosine phosphatases to decrease platelet hyper-activity; 2) Platelets induce morphological changes on CRC cells to favor migration and proliferation; 3) 3-bromopyruvate is a potential compound to target thromboembolism and pre-metastasis process in oncological patients (Faria et al, 2019). We also investigated the tumor cell-platelet interaction focused on cell biology to better understand the platelet effect on cancer cells and LMWPTP expression, on coordination of cell proliferation and migration. In summary, LMWPTP contributes for metastasis process, especially in hematogenous dissemination, and for tumor aggressiveness (AU)

• FAPESP's process: 17/08119-8 - Hematogenous tumor metastasis in colon rectal cancer cells: influence of LMWPTP and 3-bromopyruvate
• Grantee: Alessandra Valéria de Sousa Faria
• Support Opportunities: Scholarships in Brazil - Doctorate