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

[91] Capivasertib, an AKT Kinase Inhibitor, as Monotherapy or in Combination with Fulvestrant in Patients with AKT1E17K-Mutant, ER-Positive Metastatic Breast Cancer [J].

Smyth, Lillian M. ;

Tamura, Kenji ;

Oliveira, Mafalda ;

Ciruelos, Eva M. ;

Mayer, Ingrid A. ;

Sablin, Marie-Paule ;

Biganzoli, Laura ;

Ambrose, Helen J. ;

Ashton, Jack ;

Barnicle, Alan ;

Cashell, Des D. ;

Corcoran, Claire ;

de Bruin, Elza C. ;

Foxley, Andrew ;

Hauser, Joana ;

Lindemann, Justin P. O. ;

Maudsley, Rhiannon ;

McEwen, Robert ;

Moschetta, Michele ;

Pass, Martin ;

Rowlands, Vicky ;

Schiavon, Gaia ;

Banerji, Udai ;

Scaltriti, Maurizio ;

Taylor, Barry S. ;

Chandarlapaty, Sarat ;

Baselga, Jose ;

Hyman, David M. .

CLINICAL CANCER RESEARCH, 2020, 26 (15) :3947-3957

[92] Characteristics and Outcome of AKT1E17K_Mutant Breast Cancer Defined through AACR Project GENIE, a Clinicogenomic Registry [J].

Smyth, Lillian M. ;

Zhou, Qin ;

Nguyen, Bastien ;

Yu, Celeste ;

Lepisto, Eva M. ;

Arnedos, Monica ;

Hasset, Michael J. ;

Lenoue-Newton, Michele L. ;

Blauvelt, Natalie ;

Dogan, Semih ;

Micheel, Christine M. ;

Wathoo, Chetna ;

Horlings, Hugo ;

Hudecek, Jan ;

Gross, Benjamin E. ;

Kundra, Ritika ;

Sweeney, Shawn M. ;

Gao, JianJiong ;

Schultz, Nikolaus ;

Zarski, Andrew ;

Gardos, Stuart M. ;

Lee, Jocelyn ;

Sheffler-Collins, Seth ;

Park, Ben H. ;

Sawyers, Charles L. ;

Andre, Fabrice ;

Levy, Mia ;

Meric-Bernstam, Funda ;

Bedard, Philippe L. ;

Iasonos, Alexia ;

Schrag, Deborah ;

Hyman, David M. .

CANCER DISCOVERY, 2020, 10 (04) :526-535

[93] Integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer [J].

Stemke-Hale, Katherine ;

Gonzalez-Angulo, Ana Maria ;

Lluch, Ana ;

Neve, Richard M. ;

Kuo, Wen-Lin ;

Davies, Michael ;

Carey, Mark ;

Hu, Zhi ;

Guan, Yinghui ;

Sahin, Aysegul ;

Symmans, W. Fraser ;

Pusztai, Lajos ;

Nolden, Laura K. ;

Horlings, Hugo ;

Berns, Katrien ;

Hung, Mien-Chie ;

van de Vijver, Marc J. ;

Valero, Vicente ;

Gray, Joe W. ;

Bernards, Rene ;

Mills, Gordon B. ;

Hennessy, Bryan T. .

CANCER RESEARCH, 2008, 68 (15) :6084-6091

[94] The E3 Ligase TTC3 Facilitates Ubiquitination and Degradation of Phosphorylated Akt [J].

Suizu, Futoshi ;

Hiramuki, Yosuke ;

Okumura, Fumihiko ;

Matsuda, Mami ;

Okumura, Akiko J. ;

Hirata, Noriyuki ;

Narita, Masumi ;

Kohno, Takashi ;

Yokota, Jun ;

Bohgaki, Miyuki ;

Obuse, Chikashi ;

Hatakeyama, Shigetsugu ;

Obata, Toshiyuki ;

Noguchi, Masayuki .

DEVELOPMENTAL CELL, 2009, 17 (06) :800-810

[95] Safety and tolerability of AZD5363 in Japanese patients with advanced solid tumors [J].

Tamura, Kenji ;

Hashimoto, Jun ;

Tanabe, Yuko ;

Kodaira, Makoto ;

Yonemori, Kan ;

Seto, Takashi ;

Hirai, Fumihiko ;

Arita, Shuji ;

Toyokawa, Gouji ;

Chen, Lan ;

Yamamoto, Hiroshi ;

Kawata, Toshio ;

Lindemann, Justin ;

Esaki, Taito .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2016, 77 (04) :787-795

[96] TTC3 Ubiquitination Terminates Akt-ivation [J].

Toker, Alex .

DEVELOPMENTAL CELL, 2009, 17 (06) :752-754

[97] High prevalence of PIK3CA/AKT pathway mutations in papillary neoplasms of the breast [J].

Troxell, Megan L. ;

Levine, Judith ;

Beadling, Carol ;

Warrick, Andrea ;

Dunlap, Jennifer ;

Presnell, Ajia ;

Patterson, Janice ;

Shukla, Arielle ;

Olson, Neal R. ;

Heinrich, Michael C. ;

Corless, Christopher L. .

MODERN PATHOLOGY, 2010, 23 (01) :27-37

[98] Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks [J].

Uematsu, Naoya ;

Weterings, Eric ;

Yano, Ken-ichi ;

Morotomi-Yano, Keiko ;

Jakob, Burkhard ;

Taucher-Scholz, Gisela ;

Mari, Pierre-Olivier ;

van Gent, Dik C. ;

Chen, Benjamin P. C. ;

Chen, David J. .

JOURNAL OF CELL BIOLOGY, 2007, 177 (02) :219-229

[99] Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors [J].

Vasan, Neil ;

Razavi, Pedram ;

Johnson, Jared L. ;

Shao, Hong ;

Shah, Hardik ;

Antoine, Alesia ;

Ladewig, Erik ;

Gorelick, Alexander ;

Lin, Ting-Yu ;

Toska, Eneda ;

Xu, Guotai ;

Kazmi, Abiha ;

Chang, Matthew T. ;

Taylor, Barry S. ;

Dickler, Maura N. ;

Jhaveri, Komal ;

Chandarlapaty, Sarat ;

Rabadan, Raul ;

Reznik, Ed ;

Smith, Melissa L. ;

Sebra, Robert ;

Schimmoller, Frauke ;

Wilson, Timothy R. ;

Friedman, Lori S. ;

Cantley, Lewis C. ;

Scaltriti, Maurizio ;

Baselga, Jose .

SCIENCE, 2019, 366 (6466) :714-+

[100] AKT Signaling in Physiology and Disease [J].

Vasudevan, Krishna M. ;

Garraway, Levi A. .

PHOSPHOINOSITIDE 3-KINASE IN HEALTH AND DISEASE, VOL 2, 2011, 347 :105-133

← 3 4 5 6 7 8 9 10 11 12 →