Journal of Shanghai Jiao Tong University (Medical Science) >

2021 , Vol. 41 >Issue 7: 839 - 848

DOI: https://doi.org/10.3969/j.issn.1674-8115.2021.07.001

Innovative research team achievement column

Mechanism of MUC1 in the pathogenesis of HER2-positive breast cancer

  • Cheng-zhi WANG ,
  • Hua-yun DENG ,
  • Zhi PANG ,
  • Lei HUANG
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  • Department of Histoembryology, Genetics and Developmental Biology, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China

Online published: 2021-08-03

Supported by

National Nature Science Foundation of China(82073111);Innovative Research Team of High-level Local Universities in Shanghai(SSMU-ZLCX20180102)

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Abstract

Objective

·To study the role and mechanism of mucin 1 (MUC1) in the pathogenesis of HER2-positive breast cancer.

Methods

·Virus infection technology was employed to construct MT2/MUC1 and MT2/Vec/MUC1-CD overexpression cell lines; Western blotting was used to detect the expression level of relative proteins; the ability of cell proliferation, migration and sphere formation were detected by using cell counting kit-8 (CCK-8), colony formation, wound healing, transwell and sphere formation experiments respectively; inhibitor 6-AN was used to inhibit glucose-6-phosphate 1-dehydrogenase (G6PD) activity, and the proliferation of breast cancer cells was detected by CCK-8. GEPIA and Kaplan-Meier Plotter database were analyzed to figure out the relationship of HER2, MUC1 and G6PD expression with the survival of breast cancer patients.

Results

·Overexpression of MUC1 or MUC1-CD promoted the proliferation, clone formation, migration and sphere formation of MT2 HER2-positive breast cancer cells, as well as elevating the protein level of G6PD. Inhibition of G6PD activity significantly reduced cell proliferation induced by MUC1 and MUC1-CD. High level of G6PD protein in breast cancer tissues is associated with significantly lower survival of breast cancer patients.

Conclusion

·MUC1 may promote the progression of HER2-positive breast cancer by up-regulating the expression of G6PD, suggesting that inhibition of the pentose phosphate pathway may be a target for the treatment of HER2-positive breast cancer.

Key words： breast cancer; mucin 1 (MUC1); pentose phosphate pathway (PPP); glucose-6-phosphate 1-dehydrogenase (G6PD)

Cite this article

Cheng-zhi WANG , Hua-yun DENG , Zhi PANG , Lei HUANG . Mechanism of MUC1 in the pathogenesis of HER2-positive breast cancer[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2021 , 41(7) : 839 -848 . DOI: 10.3969/j.issn.1674-8115.2021.07.001

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