KDELR2-KIF20A axis facilitates bladder cancer growth and metastasis by enhancing Golgi-mediated secretion.
KDELR2-KIF20A axis facilitates bladder cancer growth and metastasis by enhancing Golgi-mediated secretion.
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DOI：
10.1186/s12575-022-00174-y
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发表时间：
2022-09-12
影响因子：
6.4
通讯作者：
Zhang, Xiaoping
中科院分区：
文献类型：
--
作者：
Meng, Xiangui;Li, Weiquan;Yuan, Hongwei;Dong, Wei;Xiao, Wen;Zhang, Xiaoping
关键词：
膀胱癌(BCA)是世界范围内一种致命的癌症，预后不良。识别新的生长和转移驱动因素具有治疗该病的潜力。内质网和高尔基体之间的运输平衡和高尔基体介导的基质金属蛋白酶(MMPs)的分泌与肿瘤的进展密切相关。然而，到目前为止，机械论的研究仍然有限。在这里，我们确定KDELR2是一个潜在的危险因素，对BCA患者，特别是那些含有KDELR2扩增的患者具有预后价值。此外，基于生物信息学分析和功能研究，我们发现KDELR2是BCA细胞增殖和致瘤性的调节因子。从机制上，我们揭示了KDELR2可以调节KIF20A的表达，从而刺激MMP2、MMP9和MKI67的表达。在功能上，KDELR2和KIF20A的过表达在体外显著促进肿瘤的增殖、迁移和侵袭，并促进体内肿瘤的生长，而KDELR2和KIF20A的过表达则起到相反的作用。KDELR2的过表达也促进了体内的淋巴转移。总之，我们的发现阐明了KDELR2-KIF20A轴增加高尔基体介导的MMPs分泌以驱动BCA肿瘤进展的迄今未知的机制。网上版载有补充材料，可在10.1186/s12575-022-00174-y查阅。
Bladder cancer (BCa) is a fatal form of cancer worldwide associated with a poor prognosis. Identifying novel drivers of growth and metastasis hold therapeutic potential for the disease. Transport homeostasis between the endoplasmic reticulum and Golgi and the secretion of matrix metalloproteinases (MMPs) mediated by Golgi have been reported to be closely associated with tumor progression. However, to date, mechanistic studies remain limited. Here, we identified KDELR2 as a potential risk factor with prognostic value in patients with BCa, especially those harbouring the KDELR2 amplification. In addition, we found that KDELR2 is a regulator of BCa cell proliferation and tumorigenicity based on bioinformatic analysis with functional studies. Mechanistically, we revealed that KDELR2 could regulate the expression of KIF20A, thus stimulating the expression of MMP2, MMP9 and MKI67. Functionally, the overexpression of KDELR2 and KIF20A markedly promoted proliferation, migration, and invasion in vitro and enhanced tumor growth in vivo, while knockdown of KDELR2 and KIF20A exerted the opposite effects. And the overexpression of KDELR2 also enhanced lymph node metastasis in vivo. Collectively, our findings clarified a hitherto unexplored mechanism of KDELR2-KIF20A axis in increasing Golgi-mediated secretion of MMPs to drive tumor progression in BCa. The online version contains supplementary material available at 10.1186/s12575-022-00174-y.
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GEPIA：用于癌症和正常基因表达谱和交互式分析的网络服务器。
影响因子：
14.9
作者：
Tang Z;Li C;Kang B;Gao G;Li C;Zhang Z
通讯作者：
Zhang Z
DOI：
10.1083/jcb.200705180
发表时间：
2007-12-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Ruddock L
影响因子：
8
作者：
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通讯作者：
Nakamura, Y
影响因子：
4.6
作者：
Blum, Andrea;Khalifa, Saleem;Schmitt, Manfred J.
通讯作者：
Schmitt, Manfred J.
影响因子：
6
作者：
Gasnereau, Isabelle;Boissan, Mathieu;Sobczak-Thepot, Joelle
通讯作者：
Sobczak-Thepot, Joelle