AUTHOR=Chen Ying , Huang Lan , Dong Yongjian , Tao Changli , Zhang Rongxin , Shao Hongwei , Shen Han 

TITLE=Effect of AKT1 (p. E17K) Hotspot Mutation on Malignant Tumorigenesis and Prognosis

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.573599

DOI=10.3389/fcell.2020.573599

ISSN=2296-634X

ABSTRACT=<p>The substitution of the seventeenth amino acid glutamate by lysine in the homologous structural domain of the Akt1 gene pleckstrin is a somatic cellular mutation found in breast, colorectal, and ovarian cancers, named p. Glu17Lys or E17K. In recent years, a growing number of studies have suggested that this mutation may play a unique role in the development of tumors. In this review article, we describe how AKT1(E17K) mutations stimulate downstream signals that cause cells to emerge transformed; we explore the differential regulation and function of E17K in different physiological and pathological settings; and we also describe the phenomenon that E17K impedes tumor growth by interfering with growth-promoting and chemotherapy-resistant AKT1<sup>low</sup>QCC generation, an intriguing finding that mutants may prolong tumor patient survival by activating feedback mechanisms and disrupting transcription. This review is intended to provide a better understanding of the role of AKT1(E17K) in cancer and to inform the development of AKT1(E17K)-based antitumor strategies.</p>