Abstract ED9-2: The contribution of the tumor microenvironment to cancer dormancy

Abstract

Abstract In this seminar I will discuss how breast cancer DTCs modify the metastatic microenvironment to favor seeding and dormancy. In order to extravasate efficiently and form metastasis, cancer cells have to become migratory and coordinate both invasive and proliferative programs at distant organs. High-resolution lattice light-sheet with adaptive optics imaging in living cells revealed that DTCs extravasate from the blood vessels by forming actin-rich invadopodium protrusions. We have identified a population of breast cancer DTCs with pro-invasive and pro-dormancy capacities. These cells downregulate srGAP1, a GTPase regulator, favoring dissemination and dormancy at metastatic organs. Our findings describe a novel mechanism mediating the shift from a proliferative to an invasive/dormant phenotype in breast cancer cells in vivo. srGAP1 is a new regulator of dormancy that regulates the formation of dormancy-permissive microenvironments through increased secretion of TGFb2 and SMAD2 activation. Citation Format: Jose Javier Bravo-Cordero. The contribution of the tumor microenvironment to cancer dormancy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED9-2.