Decoding the RAS-PI3K-YAP signalling axis in CAFs during lung cancer progression
Marta Alcón
Centro de Investigación del Cáncer (CSIC-Universidad de Salamanca)
The tumour microenvironment plays a critical role in cancer progression by shaping tumour behaviour and influencing therapeutic response. Among its components, cancer-associated fibroblasts (CAFs) actively contribute to tumour growth, invasion, extracellular matrix (ECM) remodelling, and therapy resistance. The transcriptional co- activator YAP, classically regulated by the Hippo pathway and mechanical cues, has emerged as a key determinant of fibroblast activation.
Recent data from our group show that, in CAFs, the RAS-PI3K signalling pathway regulates both the expression and transcriptional activity of YAP. Disruption of this interaction results in reduced levels of YAP, diminished expression of CAF activation markers such as α-SMA, vimentin, and tenascin C, impaired focal adhesion dynamics, and defective ECM organisation. These findings indicate that RAS-PI3K signalling plays a central role in sustaining the activated CAF phenotype.
In this seminar, we will present our ongoing research to elucidate the molecular mechanisms linking RAS-PI3K signalling to YAP regulation in CAFs, and to define the downstream transcriptional programs that control their functional states. Understanding this regulatory axis may uncover novel strategies to target tumour-stroma interactions and enhance therapeutic efficacy in cancer.