Figure 2.

Multiple sensor and effector functions of TRP channels and STIM/ORAI proteins in the tumour microenvironment. Illustration of major hypoxia and cellular oxidative stress-dependent mechanisms in cancer and stroma cells involving TRP channels and STIM/ORAI proteins. Hypoxic and oxidative stress can lead to up-regulation of TRP channels (e.g. TRPC1, TRPC3 and TRPC6) and STIM/ORAI proteins and mediate the production of ROS and ADPr. In cancer and stroma cells, TRP channels and STIM/ORAI proteins can have both a sensor function for extra-/intracellular stimuli mediating cellular responses and a effector function by increased expression and activation to induce chemokine/cytokine production in these cells. For the sake of clarity, this sketch does not include all signalling pathways mentioned in the text. Neither did we include all microenvironmental, growth factor- and chemokine-activated pathways involved in increased activation or expression of TRP channels and STIM/ORAI proteins. (Figure modified from Stock et al., 2013.)