SHP2 is essential for the progesterone-promoted proliferation and migration in breast cancer cell lines
IntroductionWe previously demonstrated that progesterone (P4) can promote breast cancer cell proliferation and migration through activating the P4 receptor (PR)/cSrc-mediated signaling pathway. It has been suggested that high level of Src homology region 2 domain-containing phosphatase-2 (SHP2) migh...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1523589/full |
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| author | Hui-Chen Wang Hui-Chen Wang Wen-Sen Lee Wen-Sen Lee Wen-Sen Lee Wen-Sen Lee |
| author_facet | Hui-Chen Wang Hui-Chen Wang Wen-Sen Lee Wen-Sen Lee Wen-Sen Lee Wen-Sen Lee |
| author_sort | Hui-Chen Wang |
| collection | DOAJ |
| description | IntroductionWe previously demonstrated that progesterone (P4) can promote breast cancer cell proliferation and migration through activating the P4 receptor (PR)/cSrc-mediated signaling pathway. It has been suggested that high level of Src homology region 2 domain-containing phosphatase-2 (SHP2) might be involved in breast oncogenesis. This study aimed to investigate whether SHP2 is involved in the P4-mediated cSrc activation in breast cancer cells.MethodsT47D, MCF-7 and BT-483 breast cancer cell lines were used in this study. Cell proliferation and migration were examined using MTT technique and wound healing assay, respectively. Immunoprecipitation assay and Western blot analysis were performed to evaluate protein-protein interaction and protein expression, respectively. Small interfering RNA (siRNA) technique was used to knock down protein expression.ResultsKnockdown of SHP2 expression abolished the P4-promoted cell proliferation and migration in T47D, MCF and BT-483 cell lines, suggesting that presence of SHP2 is essential for the P4-increased proliferation and migration of breast cancer cell lines. P4 (50 nM) treatment increased the complex formations of PR-cSrc-SHP2-caveolin-1, SHP2-p140Cap, and SHP2-Csk, and the level of p-cSrcY416 (activated form of cSrc). However, knockdown of SHP2 expression increased the complex formations of PR-cSrc-caveolin-1-Csk-p140Cap and the levels of p-caveolin-1, p-Csk and p-cSrcY527 (inactivated form of cSrc).DiscussionOur data suggest that SHP2 can bind to cSrc-negative regulatory proteins (p140Cap and Csk), hence preventing the interaction between cSrc and cSrc-negative regulatory proteins, leading to decreased phosphorylation of cSrc Y527 and prolonged cSrc activation. These findings highlight the role of SHP2 in the P4-promoted breast cancer cell proliferation and migration. |
| format | Article |
| id | doaj-art-00b6b0f404c64b7090d0a3d028558eca |
| institution | Kabale University |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj-art-00b6b0f404c64b7090d0a3d028558eca2025-02-10T05:16:22ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-02-011610.3389/fendo.2025.15235891523589SHP2 is essential for the progesterone-promoted proliferation and migration in breast cancer cell linesHui-Chen Wang0Hui-Chen Wang1Wen-Sen Lee2Wen-Sen Lee3Wen-Sen Lee4Wen-Sen Lee5Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, TaiwanSecond Degree Bachelor of Science in Nursing, College of Medicine, National Taiwan University, Taipei, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, TaiwanTaipei Cancer Center, Taipei Medical University Hospital, Taipei, TaiwanCell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, TaiwanDepartment of Physiology, School of Medicine, Tzu Chi University, Hualien, TaiwanIntroductionWe previously demonstrated that progesterone (P4) can promote breast cancer cell proliferation and migration through activating the P4 receptor (PR)/cSrc-mediated signaling pathway. It has been suggested that high level of Src homology region 2 domain-containing phosphatase-2 (SHP2) might be involved in breast oncogenesis. This study aimed to investigate whether SHP2 is involved in the P4-mediated cSrc activation in breast cancer cells.MethodsT47D, MCF-7 and BT-483 breast cancer cell lines were used in this study. Cell proliferation and migration were examined using MTT technique and wound healing assay, respectively. Immunoprecipitation assay and Western blot analysis were performed to evaluate protein-protein interaction and protein expression, respectively. Small interfering RNA (siRNA) technique was used to knock down protein expression.ResultsKnockdown of SHP2 expression abolished the P4-promoted cell proliferation and migration in T47D, MCF and BT-483 cell lines, suggesting that presence of SHP2 is essential for the P4-increased proliferation and migration of breast cancer cell lines. P4 (50 nM) treatment increased the complex formations of PR-cSrc-SHP2-caveolin-1, SHP2-p140Cap, and SHP2-Csk, and the level of p-cSrcY416 (activated form of cSrc). However, knockdown of SHP2 expression increased the complex formations of PR-cSrc-caveolin-1-Csk-p140Cap and the levels of p-caveolin-1, p-Csk and p-cSrcY527 (inactivated form of cSrc).DiscussionOur data suggest that SHP2 can bind to cSrc-negative regulatory proteins (p140Cap and Csk), hence preventing the interaction between cSrc and cSrc-negative regulatory proteins, leading to decreased phosphorylation of cSrc Y527 and prolonged cSrc activation. These findings highlight the role of SHP2 in the P4-promoted breast cancer cell proliferation and migration.https://www.frontiersin.org/articles/10.3389/fendo.2025.1523589/fullbreast cancer cell linesCskcSrcp-cSrcY416p-cSrcY527SHP2 |
| spellingShingle | Hui-Chen Wang Hui-Chen Wang Wen-Sen Lee Wen-Sen Lee Wen-Sen Lee Wen-Sen Lee SHP2 is essential for the progesterone-promoted proliferation and migration in breast cancer cell lines Frontiers in Endocrinology breast cancer cell lines Csk cSrc p-cSrcY416 p-cSrcY527 SHP2 |
| title | SHP2 is essential for the progesterone-promoted proliferation and migration in breast cancer cell lines |
| title_full | SHP2 is essential for the progesterone-promoted proliferation and migration in breast cancer cell lines |
| title_fullStr | SHP2 is essential for the progesterone-promoted proliferation and migration in breast cancer cell lines |
| title_full_unstemmed | SHP2 is essential for the progesterone-promoted proliferation and migration in breast cancer cell lines |
| title_short | SHP2 is essential for the progesterone-promoted proliferation and migration in breast cancer cell lines |
| title_sort | shp2 is essential for the progesterone promoted proliferation and migration in breast cancer cell lines |
| topic | breast cancer cell lines Csk cSrc p-cSrcY416 p-cSrcY527 SHP2 |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1523589/full |
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