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

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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.

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All data generated or analyzed during this study are included in this published article.

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Funding

This work was supported by Science and Technology Fund Project of health and Family Planning Commission of Guizhou Province in 2018 (Grant Nos. gzwjkj-2018-1-075, gzwjkj-2018-1-035), Special project of academic new seedling cultivation and innovation exploration of Guizhou Medical University in 2018 (Grant No. [2018]5779-30) and State science and technology plan project of Qiandongnan Prefecture in 2019 (Grant No. Qiandongnan Kehe J Zi [2019] No. 145, Qiandongnan Kehe J Zi [2019] No. 146).

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Authors and Affiliations

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

    Guangming Liu, Feng Hu & Junjie Qin

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

    Wei Zhan

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

    Wei Guo

  4. Department of Traditional Chinese Medicine, Guizhou Provincial People’s Hospital, No. 83 Zhongshan East Road, Guiyang, 550002, Guizhou, China

    Rui Li

  5. Department of Imaging, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Road, Guiyang, 550004, Guizhou, China

    Xin Liao

Authors
  1. Guangming Liu
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  2. Wei Zhan
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  3. Wei Guo
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  4. Feng Hu
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  5. Junjie Qin
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  6. Rui Li
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  7. Xin Liao
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Contributions

RL and XL conceived and designed the experiments, GML and WZ analyzed and interpreted the results of the experiments, WG, FH and JJQ performed the experiments.

Corresponding authors

Correspondence to Rui Li or Xin Liao.

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The authors state that there are no conflicts of interest to disclose.

Ethical Approval

This study was reviewed and approved by the Ethics Review Committee of Affiliated Hospital of Guizhou Medical University and was performed in accordance with Declaration of Helsinki. Every patient provided their informed consent in writing prior to their participation in the study. Animal protocols, housing, and care were performed with the approval of the Ethics Committee of Guizhou Medical University and conducted according to the guidelines set forth in the National Institutes of Health's (NIH) “Guide for the Care and Use of Laboratory Animals” (8th edition).

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Liu, G., Zhan, W., Guo, W. et al. MELK Accelerates the Progression of Colorectal Cancer via Activating the FAK/Src Pathway. Biochem Genet 58, 771–782 (2020). https://doi.org/10.1007/s10528-020-09974-x

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  • DOI: https://doi.org/10.1007/s10528-020-09974-x

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