Modulation of new metastasis suppressor genes in lung cancer

• Grant number: 23/18041-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2024
• End date: June 30, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Cesar Seigi Fuziwara
• Grantee: Guilherme Alves de Gois
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/17282-5 - Transcriptional and post-transcriptional control in aggressive cancer and metastasis, AP.JP

Abstract

Lung cancer is the most lethal type of cancer, and the high mortality rate is associated to the late detection of disease when most patients already have distant metastases, reducing 5-years survival to 20%. Lung oncogenesis is related to activating mutations in the MAPK signaling such as KRAS and EGFR, and inactivating mutation in the TP53 gene. However, murine models bearing these mutations develop lung adenocarcinoma but with long latency for metastases. Thus, the identification of new molecular alterations associated with tumor aggressiveness and metastatic cascade is still urgent. In this project, we used the RNAseq methodology to compare the gene expression between the metastatic adenocarcinoma cell line collected in the liver of mice (KPT4-LM), compared to control adenocarcinoma (KPT4). We identified several genes which expression was strongly repressed in the metastasis and that act as transcription factors associated to lung biology. The aim of this study is to evaluate the role of the suppressed genes in metastasis by reinducing their expression using a plasmidial approach. We hope that we can then contribute to the understanding of lung cancer metastatic process.