MELK Accelerates the Progression of Colorectal Cancer via Activating the FAK/Src Pathway
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MELK Accelerates the Progression of Colorectal Cancer via Activating the FAK/Src Pathway Guangming Liu1 · Wei Zhan2 · Wei Guo3 · Feng Hu1 · Junjie Qin1 · Rui Li4 · Xin Liao5 Received: 23 February 2020 / Accepted: 22 May 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. * Rui Li [email protected] * Xin Liao [email protected] 1
Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, Jilin, China
2
Department of Colorectal Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China
3
Department of Hematology, The First Hospital of Jilin University, Changchun 130021, Jilin, China
4
Department of Traditional Chinese Medicine, Guizhou Provincial People’s Hospital, No. 83 Zhongshan East Road, Guiyang 550002, Guizhou, China
5
Department of Imaging, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Road, Guiyang 550004, Guizhou, China
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Vol.:(0123456789)
Biochemical Genetics
Keywords MELK · Proliferation · AKT · Colorectal cancer · FAK/Src pathway
Introduction Colorectal cancer (CRC) is one of the most common malignant tumors in the world, which ranks as the third among all malignant tumors in incidence and the fourth in mortality, following the lung cancer, liver cancer and gastric cancer (Parizadeh et al. 2019; Ren et al. 2015; Behjati 2015). The high mortality rate is due to metastasis in CRC patients (Goldstein et al. 2016). For patients with metastasis, the 5-year survival rate is less than 10% (McQuade et al. 2017). Clinically, most patients undergoing radical surgery have undetected micrometastases, which is also one of the main reasons for the failure of surgical treatment and tumor recurrence (Sloothaak 2015). Meanwhile, the surgical treatm
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