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Updated: Jan 2, 2026

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane

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MELK is Upregulated in Advanced Clear Cell Renal Cell Carcinoma and Promotes Disease Progression by Phosphorylating

Han Zhang1, Pengtao Wei1, Wenwei Lv1

  • 1Urology Department, Luoyang Central Hospital, Luoyang, Henan, China.

Cell Transplantation
|December 10, 2019
PubMed

Insights

Maternal and embryonic leucine zipper kinase (MELK) drives advanced kidney cancer. Inhibiting MELK may offer a new treatment strategy for clear cell renal cell carcinoma (ccRCC) by targeting the mTORC1 pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the predominant kidney cancer subtype.
  • Advanced stage IV ccRCC remains largely incurable, necessitating research into its underlying molecular mechanisms.
  • The molecular drivers of ccRCC progression, particularly in late stages, require further elucidation.

Purpose of the Study:

  • To identify differentially expressed genes (DEGs) between early (stage I) and advanced (stage IV) ccRCC.
  • To investigate the role of maternal and embryonic leucine zipper kinase (MELK) in ccRCC progression.
  • To explore the mechanistic link between MELK and the mammalian target of rapamycin complex 1 (mTORC1) pathway in ccRCC.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GSE73731) datasets to identify DEGs.
  • In vitro loss-of-function and gain-of-function assays to assess MELK's impact on ccRCC cell phenotype.
  • Western blotting and co-immunoprecipitation to investigate MELK's interaction with the mTORC1 pathway components, specifically PRAS40 and raptor.

Main Results:

  • MELK was found to be significantly upregulated in stage IV ccRCC compared to stage I.
  • Upregulation of MELK correlated with advanced disease status in ccRCC patients.
  • MELK promotes the malignant phenotype of ccRCC cells by activating the mTORC1 pathway, specifically through phosphorylating PRAS40 and disrupting its interaction with raptor.

Conclusions:

  • MELK plays a critical role in the progression of clear cell renal cell carcinoma.
  • MELK may serve as a novel therapeutic target for ccRCC by modulating the mTORC1 pathway.
  • Targeting MELK could potentially offer a new strategy for treating advanced ccRCC.
Keywords:
MELKPRAS40clear cell renal cell carcinomadifferentially expressed genesmTORC1

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