Understanding the role of apoptosis inhibitor 5 api5 in breast cancer

Abstract

The balance between cell death and cell division is essential for the maintenance ofhomeostasis in multicellular organisms Apoptosis or programmed cell death playsa vital role in the maintenance of this homeostasis and therefore is a tightlyregulated process Deregulation of apoptosis can lead to cancer Apoptosis inhibitor5 Api5 is an inhibitor of apoptosis The molecular mechanism underlying theactivation and regulation of Api5 is yet to be thoroughly explored Api5 has beenreported to be associated with several cancers including ovarian bladder and lungcancers Studies suggest that Api5 can be used as a biomarker for ovarian andbladder cancers However the role of Api5 in breast cancer which reports thehighest number of deaths due to cancer remains unclear My project focuses oninvestigating the role of Api5 in breast cancer In vitro overexpression studies using3D breast acinar cultures demonstrated that overexpression of Api5 resulted in thetransformation of non tumorigenic breast epithelial cells with increased proliferationand various phenotypic changes Api5 knockdown affected the tumorigenic potentialand associated phenotypes of breast cancer cells Mechanistically Api5 was shownto activate FGF2 signalling possibly leading to PDK1 Akt and ERK pathwayactivation Interestingly Api5 FGF2 signalling activates PDK1 Akt cMYC axis duringthe early days of acinar morphogenesis while activation of ERK signalling occurredduring the later days Together this led to elevated proliferation migration anchorage independent growth protein synthesis and reduced apoptosis supportingthe malignant growth of Api5 overexpressing cells in silico studies using TCGA andGENT2 database demonstrated that elevated levels of Api5 transcript in breastcancers that was also associated with poor patient survival This further correlatedwith histopathological analyses of tumour samples where h newline newline