<scp>ANP</scp>32E induces tumorigenesis of triple‐negative breast cancer cells by upregulating E2F1

<jats:p>Triple‐negative breast cancer (<jats:styled-content style="fixed-case">TNBC</jats:styled-content>) lacks expression of estrogen receptor (<jats:styled-content style="fixed-case">ER</jats:styled-content>), progesterone receptor, and the <jats:styled-content style="fixed-case">HER</jats:styled-content>2 receptor; it is highly proliferative and becomes the deadliest forms of breast cancer. Effective prognostic methods and therapeutic targets for <jats:styled-content style="fixed-case">TNBC</jats:styled-content> are required to improve patient outcomes. Here, we report that acidic nuclear phosphoprotein 32 family member E (<jats:styled-content style="fixed-case">ANP</jats:styled-content>32E), which promotes cell proliferation in mammalian development, is highly expressed in <jats:styled-content style="fixed-case">TNBC</jats:styled-content> cells compared to other types of breast cancer. High expression of <jats:styled-content style="fixed-case">ANP</jats:styled-content>32E correlates significantly with worse overall survival (OS; <jats:italic>P </jats:italic><<jats:italic> </jats:italic>0.001) and higher risks of disease recurrence (<jats:italic>P </jats:italic><<jats:italic> </jats:italic>0.001) in patients with <jats:styled-content style="fixed-case">TNBC</jats:styled-content>. Univariate and multivariate Cox‐regression models show that <jats:styled-content style="fixed-case">ANP</jats:styled-content>32E is an independent prognostic factor in <jats:styled-content style="fixed-case">TNBC</jats:styled-content>. Furthermore, we discovered that <jats:styled-content style="fixed-case">ANP</jats:styled-content>32E promotes tumor proliferation <jats:italic>in vitro</jats:italic> by inducing G1/S transition, and <jats:styled-content style="fixed-case">ANP</jats:styled-content>32E inhibition suppresses tumor formation <jats:italic>in vivo</jats:italic>. By examining the expression of E2F1, cyclin E1, and cyclin E2, we discovered that <jats:styled-content style="fixed-case">ANP</jats:styled-content>32E promotes the G1/S transition by transcriptionally inducing E2F1. Taken together, our study shows that <jats:styled-content style="fixed-case">ANP</jats:styled-content>32E is an efficient prognostic marker, and it promotes the G1/S transition and induces tumorigenesis of <jats:styled-content style="fixed-case">TNBC</jats:styled-content> cells by transcriptionally inducing E2F1.</jats:p>