Api5 and FGF2: A potential tumourigenic signalling

Abstract

Cell death and cell division equilibrium are crucial for maintaining tissue homeostasis in a multicellular organism. Apoptosis plays an essential role in preserving homeostasis and hence occurs in a coordinated manner. However, inhibition of apoptosis may lead to cancer. Apoptosis Inhibitor 5 (Api5), an anti-apoptotic protein, is upregulated in various cancers such as ovarian, bladder, cervical and lung. Studies have demonstrated that altered expression of Api5 transforms breast epithelial cells, but the mechanism involved was not well elucidated. Interestingly, our study revealed that Api5 OE increases FGF2 (Fibroblast Growth Factor 2) levels at the molecular level. Histopathological analysis also showed that protein levels of Api5 and FGF2 are upregulated in Indian breast cancer patients. We have studied the mechanistic details of the change in morphology, proliferation and polarity observed upon FGF2/FGFR1 deregulation in Api5 overexpression background. Deciphering the signalling mechanism underlying Api5-FGF2 mediated breast tumourigenesis revealed that PDK1/Akt and Ras/MAPK/ERK pathway regulated multiple transformation phenotypes. PDK1/Akt enhanced proliferation and altered morphology during initial stages, whereas Ras/MAPK/ERK regulated polarity disruption, proliferation, and reduced apoptosis during later stages of morphogenesis. In conclusion, this study provides insights into the signalling mechanism regulating the transformation phenotypes associated with Api5 overexpression in a non-malignant breast epithelial cells.