Glycogen synthase kinase-3β is a pivotal mediator of cancer invasion and resistance to therapy.
Glycogen synthase kinase-3β is a pivotal mediator of cancer invasion and resistance to therapy.
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DOI：
10.1111/cas.13028
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发表时间：
2016-10
期刊：
影响因子：
5.7
通讯作者：
Minamoto T
中科院分区：
文献类型：
--
作者：
Domoto T;Pyko IV;Furuta T;Miyashita K;Uehara M;Shimasaki T;Nakada M;Minamoto T
肿瘤细胞侵袭和对治疗的抗性是癌症的最难处理的生物学特征，因此，对当前癌症研究和治疗范例最具挑战性。包括胰腺癌和胶质母细胞瘤在内的难治性癌症显示出肿瘤细胞的高度侵袭性行为与其对化疗、放疗和靶向治疗的抗性之间存在不可分割的联系。癌症的这些侵袭性特性共享不同的细胞途径，这些细胞途径通过几个分子枢纽彼此连接。越来越多的证据表明，糖原合成酶激酶（GSK）-3 β在各种癌症类型中被异常激活，这已成为潜在的治疗靶点。在许多但不是所有的癌症类型中，异常的GSK 3 β维持肿瘤细胞的存活、永生化、增殖和侵袭，同时还使它们对化疗剂和放射不敏感或具有抗性。在这里，我们回顾了描述治疗刺激/耐药性与各种癌症类型中促侵袭表型诱导之间相关性的研究。这些癌症在很大程度上对靶向GSK 3 β的治疗有反应。本文综述了GSK 3 β作为连接肿瘤侵袭和耐药途径的分子枢纽的作用，从而突出了其作为主要癌症治疗靶点的潜力。我们还讨论了GSK 3 β在确定肿瘤细胞干细胞性中的假定参与，该干细胞性是肿瘤侵袭和治疗抗性的基础，导致难治性和难治性癌症，患者结局令人沮丧。
Tumor cell invasion and resistance to therapy are the most intractable biological characteristics of cancer and, therefore, the most challenging for current cancer research and treatment paradigms. Refractory cancers, including pancreatic cancer and glioblastoma, show an inextricable association between the highly invasive behavior of tumor cells and their resistance to chemotherapy, radiotherapy and targeted therapies. These aggressive properties of cancer share distinct cellular pathways that are connected to each other by several molecular hubs. There is increasing evidence to show that glycogen synthase kinase (GSK)‐3β is aberrantly activated in various cancer types and this has emerged as a potential therapeutic target. In many but not all cancer types, aberrant GSK3β sustains the survival, immortalization, proliferation and invasion of tumor cells, while also rendering them insensitive or resistant to chemotherapeutic agents and radiation. Here we review studies that describe associations between therapeutic stimuli/resistance and the induction of pro‐invasive phenotypes in various cancer types. Such cancers are largely responsive to treatment that targets GSK3β. This review focuses on the role of GSK3β as a molecular hub that connects pathways responsible for tumor invasion and resistance to therapy, thus highlighting its potential as a major cancer therapeutic target. We also discuss the putative involvement of GSK3β in determining tumor cell stemness that underpins both tumor invasion and therapy resistance, leading to intractable and refractory cancer with dismal patient outcomes.
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DOI：
10.2174/1871520615666150716104152
发表时间：
2016-01-01
影响因子：
2.8
作者：
Kuhlmann, Jan Dominik;Kurth, Linda Hein Ina;Dubrovska, Anna
通讯作者：
Dubrovska, Anna
影响因子：
5.7
作者：
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通讯作者：
Houghton PJ
影响因子：
6.4
作者：
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Yan, Guangmei
影响因子：
11.8
作者：
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Woodgett, James R.
DOI：
10.1016/j.bbrc.2012.05.147
发表时间：
2012-07-06
影响因子：
3.1
作者：
Kawazoe, Hisashi;Bilim, Vladimir N.;Tomita, Yoshihiko
通讯作者：
Tomita, Yoshihiko