Our group is interested in understanding how cells communicate to each other and their surroundings under physiological and pathological conditions, focusing on two GPCR signaling nodes, Gαq and GRK2. The microenvironment of a cell is an organized combination of extracellular matrix (ECM), stromal tissue (blood vessels, immune cells, fibroblasts and signaling molecules) that influences the cellular phenotype through physical, mechanical, and biochemical mechanisms. We are interested in the interplay among cell types in their specific environment in two different scenarios: (1) Emerging aspects of cancer research include the interaction between tumor cells and their surrounding stroma, and how these cells can alter their metabolism to survive. However, what enables the tumour to integrate both processes to promote malignancy and metastasis? Considering the importante of GPCR in cancer and the novel role of the Gαq protein as a central regulator of the autophagic, our goals will be to investigate the involvement of Gαq as a link between both processes in the context of oral cancer (HNSCC). We will focus on assessing the importance of the GPCR-Gαq pathway in the regulation of tumor-associated stromal architecture by CAFs (tumour-associated fibroblasts), as well as its role as a regulator in the cross-modulation between exosome secretion and the different autophagic flux pathways, both fundamental mechanisms in tumour-stromal communication. (2) Homeostasis also requires intercommunication between different cell types in their tissue environment, often involving cells of the immune system. Proper functional interactions between epidermal, dermal, and immune cell infiltration are necessary for correct homeostasis in stratified epithelia (such as skin or oral tissues). We reported that GRK2 downregulation correlates with tumor malignancy in epithelial Head and Neck Squamous Cell Carcinoma (HNSCC) and increases invasion of oral cancer cells in mice. Considering that GRK2 loss in stratified epithelia induces alterations in epidermal homeostasis, an open raised question is, how is the dialogue between keratinocytes and their cellular microenvironment fine-tuned to facilitate coordinated responses to maintain homeostasis against inflammatory diseases and cancer? To answer these questions, we will use biochemical, cell biology and exosome biology techniques, different “omic” methodologies (transcriptomics, proteomics, metabolomics), high-resolution microscopy and flow cytometry, and 2D and 3D migration/invasion systems, combined with animal models with altered Gαq or GRK2 expression. Our work will contribute to the understanding of the molecular mechanisms preserving epithelial homeostasis and lead to the discovery of novel targets and treatment approaches associated with the development of HNSCC, the sixth most prevalent cancer form in the world with a very poor prognosis and patient survival