FGFR4 promotes nuclear localization of GABP to inhibit cell apoptosis in uterine leiomyosarcoma

Zhang Pei; Zhang Hengliang; Wang Yan

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FGFR4 promotes nuclear localization of GABP to inhibit cell apoptosis in uterine leiomyosarcoma

机译：FGFR4促进GABP的核定位，以抑制子宫肌肉瘤中的细胞凋亡

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Fibroblast growth factor receptor 4 (FGFR4) has been indicated as a potential "oncogene" in various types of cancer. However, the effects and underlying mechanisms of FGFR4 on uterine leiomyosarcoma (ULMS) progression remain unclear. In this study, we firstly discovered that FGFR4 was upregulated in ULMS specimens and cell lines and closely associated with poor prognosis of ULMS patients. Cell viability and apoptosis assays showed that FGFR4 deletion inhibited cell proliferation and promoted cell apoptosis. Moreover, FGFR4 silence increased cytoplasmic GABP (GA binding protein) expression, while it decreased the nuclear GABP level to inhibit nuclear localization of GABP. Mechanistically, the inhibition ability of FGFR4 silence on nuclear localization of GABP was mediated via mammalian Ste20-like kinases 1 (MST1) activation, which could promote phosphorylation of large tumor suppressor 1 (LATS1) to reduce nuclear localization of GABP. Gain- and loss-of-functional assays indicated that FGFR4 promoted nuclear localization of GABP to inhibit cell apoptosis in ULMS. In conclusion, our findings indicated that FGFR4 inhibited cell apoptosis in ULMS via the promotion of MST1/LATS1-mediated GABP nuclear localization, shedding light on the underlying mechanism of FGFR4-induced ULMS progression.

机译：成纤维细胞生长因子受体4（FGFR4）在各种类型的癌症中被认为是一个潜在的“癌基因”。然而，FGFR4对子宫平滑肌肉瘤（ULMS）进展的影响和潜在机制尚不清楚。在本研究中，我们首次发现FGFR4在ULMS标本和细胞系中上调，并与ULMS患者的不良预后密切相关。细胞活力和凋亡检测表明，FGFR4缺失抑制细胞增殖，促进细胞凋亡。此外，FGFR4沉默增加了细胞质GABP（GA结合蛋白）的表达，同时降低了核GABP水平以抑制GABP的核定位。从机制上讲，FGFR4沉默对GABP核定位的抑制能力是通过哺乳动物Ste20样激酶1（MST1）激活介导的，它可以促进大肿瘤抑制因子1（LATS1）的磷酸化，从而降低GABP的核定位。功能获得和功能丧失分析表明，FGFR4促进GABP的核定位，从而抑制ULMS中的细胞凋亡。总之，我们的研究结果表明，FGFR4通过促进MST1/LATS1介导的GABP核定位抑制ULMS中的细胞凋亡，从而阐明FGFR4诱导ULMS进展的潜在机制。

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来源
《Cell and Tissue Research》 |2021年第2期|共15页
作者
Zhang Pei; Zhang Hengliang; Wang Yan;
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作者单位

Henan Univ Sci &

Technol Dept Gynaecol Affiliated Hosp 1 24 Jinghua Rd Luoyang City 471000;

Henan Univ Sci &

Technol Coll Clin Med 24 Jinghua Rd Luoyang City 471000 Henan Peoples R China;

Henan Univ Sci &

Technol Dept Gynaecol Affiliated Hosp 1 24 Jinghua Rd Luoyang City 471000;

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正文语种 eng
中图分类细胞生物学;
关键词
FGFR4; MST1; LATS1; GABP; Nuclear localization; Uterine leiomyosarcoma;

机译：FGFR4;MST1;LATS1;GABP;核定位;子宫leiomyosarcoma;

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FGFR4 promotes nuclear localization of GABP to inhibit cell apoptosis in uterine leiomyosarcoma

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