子宫内膜癌中 P21 激活激酶的时空定位

IF 3.2 4区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Joydeep Roy, Nagarajan Hemavathy, Roshni Saravanan, Prarthana Gopinath, Pooja Pugazh, Jeyakanthan Jeyaraman, Ganesh Venkatraman, Suresh Kumar Rayala
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引用次数: 0

摘要

子宫内膜癌是第六大常见的妇科癌症,有报道称它是由于某些抗癌药物的特异性作用而导致的恶性肿瘤。他莫昔芬是治疗 ER 阳性乳腺癌的首选药物,多项研究显示这些患者的无病生存率更高。然而,长期使用他莫昔芬与耐药性和子宫内膜恶性肿瘤的风险有关。他莫昔芬诱导子宫内膜肿瘤发生的直接机理基础尚不清楚。子宫内膜癌中 PAK1 的过度激活与总生存率低有关。本研究表明,他莫昔芬治疗可诱导 PAK1 在子宫内膜癌细胞中核定位。这种核转移是通过 JAK2 磷酸化 PAK1 和结合 β-PIX 介导的。此外,还采用了一种计算方法,包括对磷酸化和未磷酸化形式的PAK1进行分子建模和模拟,以阐明核定位的动态变化。因此,PAK1被JAK2磷酸化是其核定位和对子宫内膜癌细胞产生致瘤作用的先决条件。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Spatio-temporal localization of P21-activated kinase in endometrial cancer.

Endometrial cancer is the sixth most common gynecologic cancer, and has been reported as a malignancy arising due to the idiopathic effects of certain anticancer agents. Tamoxifen is the drug of choice in ER-positive breast cancer, and several studies have shown better disease-free survival in these patients. However, the long-term usage of tamoxifen has been associated with resistance and risk for endometrial malignancy. A direct mechanistic basis for tamoxifen-induced endometrial tumorigenesis is still unclear. Hyperactivation of PAK1 in endometrial cancer correlates with poor overall survival. The present study demonstrates that tamoxifen treatment induces nuclear localization of PAK1 in endometrial carcinoma cells. This nuclear transit is mediated through JAK2 phosphorylation of PAK1 and binding of β-PIX. In addition, a computational approach involving molecular modeling and simulation of phosphorylated and unphosphorylated forms of PAK1 was used to elucidate the dynamics of nuclear localization. Thus, PAK1 phosphorylation by JAK2 is a prerequisite for its nuclear localization and its tumorigenic effects on endometrial cancer cells.

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来源期刊
Biotechnology and applied biochemistry
Biotechnology and applied biochemistry 工程技术-生化与分子生物学
CiteScore
6.00
自引率
7.10%
发文量
117
审稿时长
3 months
期刊介绍: Published since 1979, Biotechnology and Applied Biochemistry is dedicated to the rapid publication of high quality, significant research at the interface between life sciences and their technological exploitation. The Editors will consider papers for publication based on their novelty and impact as well as their contribution to the advancement of medical biotechnology and industrial biotechnology, covering cutting-edge research in synthetic biology, systems biology, metabolic engineering, bioengineering, biomaterials, biosensing, and nano-biotechnology.
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