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

被引：36

作者：

Chen, Ying ^{[1
]}

Huang, Lan ^{[1
]}

Dong, Yongjian ^{[1
]}

Tao, Changli ^{[1
]}

Zhang, Rongxin ^{[1
]}

Shao, Hongwei ^{[1
]}

Shen, Han ^{[1
]}

机构：

[1] Guangdong Pharmaceut Univ, Sch Life Sci & Biopharmaceut, Guangdong Prov Key Lab Biotechnol Drug Candidates, Guangzhou, Peoples R China

来源：

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2020年 / 8卷

基金：

中国国家自然科学基金;

关键词：

AKT1; E17K; mutation; cancer; prognisis; PLECKSTRIN HOMOLOGY DOMAIN; KINASE INHIBITOR P27(KIP1); SQUAMOUS-CELL CARCINOMA; E3; LIGASE; ONCOGENIC MUTATION; PIK3CA MUTATIONS; HUMAN BREAST; AKT1(E17K) MUTATIONS; ACTIVATING MUTATION; INSULIN-RECEPTOR;

D O I：

10.3389/fcell.2020.573599

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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(low)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.

引用

页数：12

共 112 条

[1] PIK3CA mutations are mutually exclusive with PTEN loss in diffuse large B-cell lymphoma [J].