JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE) ›› 2021, Vol. 41 ›› Issue (7): 839-848.doi: 10.3969/j.issn.1674-8115.2021.07.001

• Innovative research team achievement column •     Next Articles

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

Cheng-zhi WANG(), Hua-yun DENG, Zhi PANG, Lei HUANG()   

  1. Department of Histoembryology, Genetics and Developmental Biology, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China
  • Online:2021-07-28 Published:2021-08-03
  • Contact: Lei HUANG E-mail:1805490350@qq.com;huanglei@shsmu.edu.cn
  • Supported by:
    National Nature Science Foundation of China(82073111);Innovative Research Team of High-level Local Universities in Shanghai(SSMU-ZLCX20180102)

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)

CLC Number: