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MELK 通过激活 FAK/Src 通路加速结直肠癌的进展。

MELK Accelerates the Progression of Colorectal Cancer via Activating the FAK/Src Pathway.

机构信息

Department of Gastroenterology, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.

Department of Colorectal Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, Guizhou, China.

出版信息

Biochem Genet. 2020 Oct;58(5):771-782. doi: 10.1007/s10528-020-09974-x. Epub 2020 May 29.

Abstract

Maternal embryo leucine zipper kinase (MELK) has a higher expression level in a variety of cancers and involved in progression of colorectal cancer. The MELK expression levels in colorectal cancer tissues and cells were detected by RT-qPCR. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and transwell assays were used to examine the effect of the MELK konckdown on the proliferation, migration and invasion of colorectal cancer cells. Western blot analysis was used to detect the protein level of MELK and the downstream signaling pathways related proteins. Our findings indicated that MELK expression in colorectal cancer tissues was significantly higher than that in para-carcinoma tissues. Knockdown of MELK with shRNA had strong inhibition effects on the proliferation, migration and invasion of colorectal cancer cells. MELK knockdown could also decrease the phosphorylation level of AKT through FAK/Src pathway. Our results indicated downregulation of MELK retarded the progression of CRC by inhibition of the phosphorylation level of AKT through inactivating FAK/Src pathways. Therefore, MELK has the potential to be explored as a new therapeutic target and knockdown can be used as a potential treatment strategy for colorectal cancer.

摘要

母源胚胎亮氨酸拉链激酶(MELK)在多种癌症中表达水平较高,并且参与结直肠癌的进展。通过 RT-qPCR 检测结直肠癌组织和细胞中的 MELK 表达水平。MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐)和 Transwell 测定用于检测 MELK konckdown 对结直肠癌细胞增殖、迁移和侵袭的影响。Western blot 分析用于检测 MELK 及其下游信号通路相关蛋白的蛋白水平。我们的研究结果表明,结直肠癌组织中的 MELK 表达明显高于癌旁组织。shRNA 敲低 MELK 对结直肠癌细胞的增殖、迁移和侵袭具有强烈的抑制作用。MELK 敲低还可以通过 FAK/Src 通路降低 AKT 的磷酸化水平。我们的结果表明,下调 MELK 通过抑制 FAK/Src 通路失活来降低 AKT 的磷酸化水平,从而延缓 CRC 的进展。因此,MELK 有可能被探索为一种新的治疗靶点,敲低可以作为结直肠癌的潜在治疗策略。

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