RT Journal Article
SR Electronic
T1 Altered expression of Api5 affects breast carcinogenesis by modulating FGF2 signalling
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.02.466904
DO 10.1101/2021.11.02.466904
A1 K Abhijith
A1 Debiprasad Panda
A1 Radhika Malaviya
A1 Gautami Gaidhani
A1 Mayurika Lahiri
YR 2021
UL http://biorxiv.org/content/early/2021/11/02/2021.11.02.466904.abstract
AB Apoptosis or programmed cell death plays a vital role in maintaining homeostasis and, therefore, is a tightly regulated process. Deregulation of apoptosis signalling can favour carcinogenesis. Apoptosis inhibitor 5 (Api5), an inhibitor of apoptosis, is upregulated in cancers. Interestingly, Api5 is shown to regulate both apoptosis and cell proliferation. To address the precise functional significance of Api5 in carcinogenesis here we investigate the role of Api5 in breast carcinogenesis.Consistently, in-silico analysis revealed elevated levels of Api5 transcript in breast cancer patients which correlated with poor prognosis. Overexpression of Api5 in non-tumorigenic breast acinar cultures resulted in increased proliferation and cells exhibited a partial EMT-like phenotype with higher migratory potential and disruption in cell polarity. Furthermore, during acini development, the influence of Api5 is mediated via the combined action of FGF2 activated PDK1-Akt/cMYC signalling and Ras-ERK pathways. Conversely, Api5 knock-down downregulated FGF2 signalling leading to reduced proliferation and diminished in vivo tumorigenic potential of the breast cancer cells. Thus, taken together, our study identifies Api5 as a central player involved in regulating multiple events during breast carcinogenesis.Competing Interest StatementThe authors have declared no competing interest.