PKM2 promotes cell metastasis and inhibits autophagy via the JAK/STAT3 pathway in hepatocellular carcinoma

Molecular and Cellular Biochemistry (2021)Cite this article

Abstract

Pyruvate kinase M2 (PKM2) is a member of the pyruvate kinase family. It has been recently reported that PKM2 displays non-metabolic activities. Nevertheless, understanding of the role of PKM2 in hepatocellular carcinoma (HCC) is insufficient. Therefore, our study aimed at exploring the impact of PKM2 on malignant growth, autophagy as well as invasion in HCC. Expression of PKM2 in HCC specimens was examined by qRT-PCR and western blot. PKM2 knock down was generated in vitro by shRNA. Activities of malignant cells as well as downstream pathways were assessed. The MTT assay was carried out to evaluate HCC proliferation, and the FACS assay was conducted to study cell death. Elevated PKM2 levels were observed in HCC samples. Knockdown (KD) of PKM2 triggered apoptosis as well as autophagy and inhibited migration and proliferation of HCC cells. Furthermore, PKM2 KD reinforced JAK/STAT3 pathway stimulation. STAT3 inhibition counteracted the impact of PKM2 on proliferation, autophagy, migration as well as cell death in HCC. To conclude, the findings of our research suggest that PKM2 reinforced metastasis and inhibited autophagy in HCC through the JAK/STAT3 pathway, and that PKM2 could serve as a promising target for HCC treatment.

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  1. Zhi Yu and Dan Wang have been contributed equally to this work and should be considered as equal first coauthors.

Affiliations

  1. Digestive Department, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, No. 100 Hong Kong Road, Jiang’an District, Wuhan, 430015, China

    Zhi Yu, Dan Wang & Yingying Tang

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  1. Zhi Yu
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  2. Dan Wang
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Correspondence to Yingying Tang.

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Yu, Z., Wang, D. & Tang, Y. PKM2 promotes cell metastasis and inhibits autophagy via the JAK/STAT3 pathway in hepatocellular carcinoma. Mol Cell Biochem (2021). https://doi.org/10.1007/s11010-020-04041-w

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Keywords

  • Apoptosis
  • Autophagy
  • Hepatocellular carcinoma
  • JAK/STAT3
  • PKM2