Carbonic Anhydrase IX Interactome and the Regulation of Cancer Progression

Solid tumours are characterized by poor vasculature, which presents a hypoxic and nutrient-deprived environment for cancer cells. To adapt and survive in these conditions, cancer cells undergo metabolic rewiring to actively acquire and utilize nutrients. Efficient pH regulatory mechanisms establish an alkaline intracellular and acidic extracellular pH that is favourable for tumour progression. A major player in this pH regulatory mechanism is carbonic anhydrase IX (CAIX), a metalloenzyme that mediates the reversible hydration of carbon dioxide. CAIX is expressed in several solid tumours and is a marker of poor prognosis and response to therapy. Multiple pre-clinical studies have elucidated the role of CAIX in promoting various stages of tumour progression. We recently performed an unbiased proteomic screen to identify the interactome of CAIX using proximity-dependent biotin identification (BioID) technique. In this chapter, we illustrate a comprehensive analysis of the CAIX interactome by classifying the interactors based on cellular functions. Furthermore, we discuss the role of some of these interactions that are involved in the metastatic cascade and metabolic adaptation of cancer cells.