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

doi:10.3969/j.issn.1674-8115.2021.07.001

Abstract

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:

R737.9

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 JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(7): 839-848.

Figures/Tables 6

Fig 1 Expression of MUC1 was detected by Western blotting

Fig 2 MUC1 promotes breast cancer cell proliferation and colony formation ability

Fig 3 MUC1 promotes breast cancer cell migration

Fig 4 MUC1 increases the sphere formation of breast cancer cells

Fig 5 G6PD is involved in the proliferation of breast cancer cells induced by MUC1

Fig 6 Database analysis of the expression of G6PD and survival

TrendMD

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