El entorno tumoral como regulador de la carcinogénesis: Interacciones con la membrana basal y células adyacentes

Abstract

Cancer progression depends not only on cell-intrinsic alterations but also on interactions with the surrounding microenvironment. Using the Drosophila melanogaster wing imaginal disc, this thesis investigates two complementary aspects of tumor biology: First, it tries to understand the role of the crosstalk between the tumor and its ECM by studying the role of integrins and tensins in modulating RasV12 -induced tumor growth in the epithelium. Second, it studies the impact of these tumors on adjacent mesodermal cells, the Adult Muscle Precursors (AMPs). Loss of integrins enhances tumor overgrowth by increasing cell size and inducing G2 arrest, promoting non-autonomous apoptosis and local invasion through JNK activation. Conversely, tensins (blistery and PVRAP) limit RasV12 -driven growth by regulating cell proliferation and morphology without triggering JNK or invasiveness, indicating distinct but complementary tumor-suppressive roles. In the tumor microenvironment, AMPs remain viable and non-proliferative, but exhibit altered division patterns, reduced compactness, and transcriptional reprogramming involving vesicle trafficking and secretion. Despite these changes, cytoneme structure and Notch signaling remain unaffected. Notably, tumors induce localized enrichment of extracellular matrix components laminin and perlecan, likely secreted by ectodermal cells. Together, these findings highlight the dual role of integrin-related pathways in restraining tumor progression and demonstrate how epithelial tumors subtly reshape neighboring mesodermal tissue without direct transformation.