The role of PI3'-lipid signalling in melanoma initiation, progression and maintenance.
The role of PI3'-lipid signalling in melanoma initiation, progression and maintenance.
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DOI：
10.1111/exd.14489
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发表时间：
2022-01
影响因子：
3.6
通讯作者：
McMahon M
中科院分区：
文献类型：
--
作者：
Parkman GL;Foth M;Kircher DA;Holmen SL;McMahon M
磷脂酰肌醇 - 3’ - 激酶（PI3Ks）是一类脂质激酶，可将磷脂酰肌醇（PI）肌醇环上的3’羟基（OH）磷酸化。通过其下游效应分子，PI3K生成的脂质（以下简称PI3K - 脂质），如PI(3,4,5)P3和PI(3,4)P2，在正常细胞和癌细胞中调节众多生化和生物学过程，包括对生长激素和细胞因子的反应、细胞分裂周期、细胞死亡、细胞生长、血管生成、膜动力学、自噬以及细胞代谢的许多方面。受体酪氨酸激酶与其相应配体结合，会激活I类PI3’ - 激酶家族成员（PI3Kα、β、δ和γ），导致PI3K - 脂质积累。重要的是，PI3K - 脂质的积累会受到多种PI3K - 脂质磷酸酶水解作用的拮抗，其中最显著的是黑色素瘤抑制因子PTEN（脂质磷酸酶和张力蛋白同源物）。在PI3K - 脂质生成的下游，蛋白激酶AKT1 - 3被认为是细胞中PI3’ - 激酶信号传导的关键效应分子。事实上，在临床前模型中，PI3K→AKT信号轴的激活与诸如BRAFV600E癌蛋白激酶表达等改变协同作用，促进黑色素瘤的进展和转移。在这篇综述中，我们描述了不同类别的PI3K - 脂质效应分子，以及它们如何促进黑色素瘤的发生、影响肿瘤微环境、黑色素瘤的维持以及向转移性疾病的进展。我们还提供了美国食品药品监督管理局（FDA）批准的或正在进行实验的PI3K→AKT通路抑制剂的最新情况，这些抑制剂目前正在临床前模型或临床试验中进行治疗黑色素瘤的评估。
Phosphatidylinositol-3’-kinases (PI3Ks) are a family of lipid kinases that phosphorylate the 3’ hydroxyl (OH) of the inositol ring of phosphatidylinositides (PI). Through their downstream effectors, PI3K generated lipids (PI3K-lipids hereafter) such as PI(3,4,5) P3 and PI(3,4)P2 regulate myriad biochemical and biological processes in both normal and cancer cells including responses to growth hormones and cytokines; the cell division cycle; cell death; cellular growth; angiogenesis; membrane dynamics; and autophagy and many aspects of cellular metabolism. Engagement of receptor tyrosine kinase by their cognate ligands leads to activation of members of the Class I family of PI3’-kinases (PI3Kα, β, δ & γ) leading to accumulation of PI3K-lipids. Importantly, PI3K-lipid accumulation is antagonized by the hydrolytic action of a number of PI3K-lipid phosphatases, most notably the melanoma suppressor PTEN (lipid phosphatase and tensin homologue). Downstream of PI3K-lipid production, the protein kinases AKT1-3 are believed to be key effectors of PI3’-kinase signalling in cells. Indeed, in preclinical models, activation of the PI3K→AKT signalling axis cooperates with alterations such as expression of the BRAFV600E oncoprotein kinase to promote melanoma progression and metastasis. In this review, we describe the different classes of PI3K-lipid effectors, and how they may promote melanomagenesis, influence the tumour microenvironment, melanoma maintenance and progression to metastatic disease. We also provide an update on both FDA-approved or experimental inhibitors of the PI3K→AKT pathway that are currently being evaluated for the treatment of melanoma either in preclinical models or in clinical trials.
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DOI：
10.1042/bj20111741
发表时间：
2012-02-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Berenjeno IM;Guillermet-Guibert J;Pearce W;Gray A;Fleming S;Vanhaesebroeck B
通讯作者：
Vanhaesebroeck B
影响因子：
50.3
作者：
Castel P;Ellis H;Bago R;Toska E;Razavi P;Carmona FJ;Kannan S;Verma CS;Dickler M;Chandarlapaty S;Brogi E;Alessi DR;Baselga J;Scaltriti M
通讯作者：
Scaltriti M
人类癌症中的磷酸肌醇3-激酶途径：遗传改变和治疗意义。
影响因子：
2.6
作者：
Arcaro A;Guerreiro AS
通讯作者：
Guerreiro AS
影响因子：
64.8
作者：
Berger, Michael F.;Hodis, Eran;Heffernan, Timothy P.;Deribe, Yonathan Lissanu;Lawrence, Michael S.;Protopopov, Alexei;Ivanova, Elena;Watson, Ian R.;Nickerson, Elizabeth;Ghosh, Papia;Zhang, Hailei;Zeid, Rhamy;Ren, Xiaojia;Cibulskis, Kristian;Sivachenko, Andrey Y.;Wagle, Nikhil;Sucker, Antje;Sougnez, Carrie;Onofrio, Robert;Ambrogio, Lauren;Auclair, Daniel;Fennell, Timothy;Carter, Scott L.;Drier, Yotam;Stojanov, Petar;Singer, Meredith A.;Voet, Douglas;Jing, Rui;Saksena, Gordon;Barretina, Jordi;Ramos, Alex H.;Pugh, Trevor J.;Stransky, Nicolas;Parkin, Melissa;Winckler, Wendy;Mahan, Scott;Ardlie, Kristin;Baldwin, Jennifer;Wargo, Jennifer;Schadendorf, Dirk;Meyerson, Matthew;Gabriel, Stacey B.;Golub, Todd R.;Wagner, Stephan N.;Lander, Eric S.;Getz, Gad;Chin, Lynda;Garraway, Levi A.
通讯作者：
Garraway, Levi A.
DOI：
10.1158/1078-0432.ccr-14-1826
发表时间：
2015-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Carson CC;Moschos SJ;Edmiston SN;Darr DB;Nikolaishvili-Feinberg N;Groben PA;Zhou X;Kuan PF;Pandey S;Chan KT;Jordan JL;Hao H;Frank JS;Hopkinson DA;Gibbs DC;Alldredge VD;Parrish E;Hanna SC;Berkowitz P;Rubenstein DS;Miller CR;Bear JE;Ollila DW;Sharpless NE;Conway K;Thomas NE
通讯作者：
Thomas NE