|Table of Contents|

Targeting SHMT2 to up-regulate the expression of ESR1 enhances the anti-breast cancer effect of tamoxifen

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 20
Page:
3834-3840
Research Field:
Publishing date:

Info

Title:
Targeting SHMT2 to up-regulate the expression of ESR1 enhances the anti-breast cancer effect of tamoxifen
Author(s):
WANG Luwei1; BI Xianxia1; KONG Haoran2; MO Fei2; WANG Yingjie2; HU Jinxia2; QIN Yue1
1.Peninsula Cancer Center of Binzhou Medical University,Shandong Yantai 264003,China;2.Department of Biochemistry and Molecular Biology,Binzhou Medical College,Shandong Yantai 264003,China.
Keywords:
breast cancer; SHMT2; ESR1; tamoxifen; proliferation; migration
PACS:
R737.9
DOI:
10.3969/j.issn.1672-4992.2024.20.003
Abstract:
Objective:To investigate the correlation between the expression of SHMT2 and ESR1 in breast cancer tissues,and to investigate the effect of targeting SHMT2 on the treatment of breast cancer with tamoxifen.Methods:The expression of SHMT2 in breast cancer cells was analyzed with online tools and verified by immunohistochemistry.The correlation and clinical significance of SHMT2 and ESR1 expression were analyzed.MCF-7 and T47D were selected as cell models,knock down of SHMT2 was performed using RNAi,SHMT2 activity was inhibited with small molecule compound SHIN2,qRT-PCR and Western blot were used to detect the expression of ESR1.Colony formation assay was carried for detect the effects of siRNA knockdown,tamoxifen treatment,or siRNA combined with tamoxifen on proliferation of breast cancer cells.Transwell assay was used to detect the effects of SHMT2 targeted inhibitors SHIN2,tamoxifen,and the combination of SHIN2 and tamoxifen treatment on cell migration.Results:Bioinformatics analysis revealed that SHMT2 was highly expressed in breast cancer tissues,and the higher expression of SHMT2 in ER positive breast cancer was correlated with poor prognosis of patients.Knockdown or inhibition of SHMT2 activity lead to the up-regulation of ESR1,and tamoxifen combined with siRNA or SHIN2 has a stronger inhibitory effect on the proliferation and migration of breast cancer cells.Conclusion:There is a negative correlation between the expression of SHMT2 and ESR1 in breast cancer tissue.Targeting or inhibiting of SHMT2 activity can up-regulate ESR1 expression and enhance the anti-breast cancer effect of tamoxifen.

References:

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Memo

Memo:
National Natural Science Foundation of China(No.81502536）；国家自然科学基金（编号：81502536）；山东省自然科学基金面上项目（编号：ZR2020MH218,ZR2023MH367）；山东省大学生科技创新项目（编号：S202310440199,S202210440046）
Last Update: 1900-01-01