Fig. 8: Proposed model of homophilic ATP1A1 interactions trigger activin A secretion to promote EMT of tumor cells and myofibroblast activation for tumor invasion and metastasis.

Homophilic ATP1A1 interactions between ATP1A1-overexpressing tumor cells and fibroblasts stabilize ATP1A1 on fibroblasts leading to calcium oscillations, NF-κB activation, and activin A secretion. High concentration of activin A along tumor-stromal interface induces EMT of tumor cells for tumor invasion and metastasis. On the other hand, autocrine activin A activates a subpopulation of peri-tumoral αSMA+ myofibroblast.