SHMT2 Promotes Invasion and Migration of Breast Cancer Cells Through Binding to and Up-regulating HAX1
Objective To explore the molecular mechanism of SHMT2 regulating the invasion and migration of breast cancer cells. Methods Bioinformatics analysis was used to verify the role of SHMT2 in breast cancer tissues. Transwell assay was used to detect the changes of invasion and migration abilities of bre...
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| Format: | Article |
| Language: | zho |
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Magazine House of Cancer Research on Prevention and Treatment
2023-09-01
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| Series: | Zhongliu Fangzhi Yanjiu |
| Subjects: | |
| Online Access: | http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.23.0462 |
| _version_ | 1797671709444145152 |
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| author | CHEN Qianzhi SHEN Na ZHANG Ning CHEN Yan |
| author_facet | CHEN Qianzhi SHEN Na ZHANG Ning CHEN Yan |
| author_sort | CHEN Qianzhi |
| collection | DOAJ |
| description | Objective To explore the molecular mechanism of SHMT2 regulating the invasion and migration of breast cancer cells. Methods Bioinformatics analysis was used to verify the role of SHMT2 in breast cancer tissues. Transwell assay was used to detect the changes of invasion and migration abilities of breast cancer cells. Co-immunoprecipitation, knockdown plasmid transfection and Western blot were used to determine the regulatory relationship between different proteins. Results Bioinformatics analysis showed that the expression level of SHMT2 in invasive breast cancer tissues was significantly higher than that in adjacent normal tissues (P < 0.001). The 5-year disease-specific survival and overall survival in the SHMT2 high expression group were significantly lower than those in the SHMT2 low expression group (both P < 0.001). Transwell assay showed that SHMT2 knockdown significantly reduced the invasion ability (t=5.375, P=0.0058) and migration ability (t=6.274, P=0.0033) of MCF7 cells. Western blot showed that SHMT2 could combine to HAX1, and knockdown of SHMT2 reduced the protein level of HAX1. Transwell assay showed that the inhibitory effect of SHMT2 knockdown on the migration of MCF7 cells could be reversed by overexpression of HAX1 (t=6.274, P=0.0033; t=8.041, P=0.0013), while SHMT2 inhibitor (SHIN1, 10 nmol/L) significantly inhibited the migration of MCF7 cells induced by SHMT2 overexpression (t=10.16, P=0.0005; t=8.741, P=0.0009). Conclusion SHMT2 was closely related to the poor prognosis of breast cancer, and was a key factor in the invasion and migration of breast cancer cells. The mechanism was that SHMT2 increased the invasion and migration ability of breast cancer cells by binding to and up-regulating HAX1. It was verified that SHMT2 inhibitor could significantly reduce the migration ability of breast cancer cells. This study explored the therapeutic potential of SHMT2 inhibitor in metastatic breast cancer, and found potential intervention targets for its clinical treatment. |
| first_indexed | 2024-03-11T21:19:32Z |
| format | Article |
| id | doaj.art-03c2eaef3497451da80845115304b098 |
| institution | Directory Open Access Journal |
| issn | 1000-8578 |
| language | zho |
| last_indexed | 2024-03-11T21:19:32Z |
| publishDate | 2023-09-01 |
| publisher | Magazine House of Cancer Research on Prevention and Treatment |
| record_format | Article |
| series | Zhongliu Fangzhi Yanjiu |
| spelling | doaj.art-03c2eaef3497451da80845115304b0982023-09-28T08:05:30ZzhoMagazine House of Cancer Research on Prevention and TreatmentZhongliu Fangzhi Yanjiu1000-85782023-09-0150986086510.3971/j.issn.1000-8578.2023.23.04628578.2023.23.0462SHMT2 Promotes Invasion and Migration of Breast Cancer Cells Through Binding to and Up-regulating HAX1CHEN Qianzhi0SHEN Na1ZHANG Ning2CHEN Yan3Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaObjective To explore the molecular mechanism of SHMT2 regulating the invasion and migration of breast cancer cells. Methods Bioinformatics analysis was used to verify the role of SHMT2 in breast cancer tissues. Transwell assay was used to detect the changes of invasion and migration abilities of breast cancer cells. Co-immunoprecipitation, knockdown plasmid transfection and Western blot were used to determine the regulatory relationship between different proteins. Results Bioinformatics analysis showed that the expression level of SHMT2 in invasive breast cancer tissues was significantly higher than that in adjacent normal tissues (P < 0.001). The 5-year disease-specific survival and overall survival in the SHMT2 high expression group were significantly lower than those in the SHMT2 low expression group (both P < 0.001). Transwell assay showed that SHMT2 knockdown significantly reduced the invasion ability (t=5.375, P=0.0058) and migration ability (t=6.274, P=0.0033) of MCF7 cells. Western blot showed that SHMT2 could combine to HAX1, and knockdown of SHMT2 reduced the protein level of HAX1. Transwell assay showed that the inhibitory effect of SHMT2 knockdown on the migration of MCF7 cells could be reversed by overexpression of HAX1 (t=6.274, P=0.0033; t=8.041, P=0.0013), while SHMT2 inhibitor (SHIN1, 10 nmol/L) significantly inhibited the migration of MCF7 cells induced by SHMT2 overexpression (t=10.16, P=0.0005; t=8.741, P=0.0009). Conclusion SHMT2 was closely related to the poor prognosis of breast cancer, and was a key factor in the invasion and migration of breast cancer cells. The mechanism was that SHMT2 increased the invasion and migration ability of breast cancer cells by binding to and up-regulating HAX1. It was verified that SHMT2 inhibitor could significantly reduce the migration ability of breast cancer cells. This study explored the therapeutic potential of SHMT2 inhibitor in metastatic breast cancer, and found potential intervention targets for its clinical treatment.http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.23.0462breast cancershmt2shmt2 inhibitorhax1invasionmigration |
| spellingShingle | CHEN Qianzhi SHEN Na ZHANG Ning CHEN Yan SHMT2 Promotes Invasion and Migration of Breast Cancer Cells Through Binding to and Up-regulating HAX1 Zhongliu Fangzhi Yanjiu breast cancer shmt2 shmt2 inhibitor hax1 invasion migration |
| title | SHMT2 Promotes Invasion and Migration of Breast Cancer Cells Through Binding to and Up-regulating HAX1 |
| title_full | SHMT2 Promotes Invasion and Migration of Breast Cancer Cells Through Binding to and Up-regulating HAX1 |
| title_fullStr | SHMT2 Promotes Invasion and Migration of Breast Cancer Cells Through Binding to and Up-regulating HAX1 |
| title_full_unstemmed | SHMT2 Promotes Invasion and Migration of Breast Cancer Cells Through Binding to and Up-regulating HAX1 |
| title_short | SHMT2 Promotes Invasion and Migration of Breast Cancer Cells Through Binding to and Up-regulating HAX1 |
| title_sort | shmt2 promotes invasion and migration of breast cancer cells through binding to and up regulating hax1 |
| topic | breast cancer shmt2 shmt2 inhibitor hax1 invasion migration |
| url | http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.23.0462 |
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