Her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of MAP3K4
Abstract Early dissemination refers to the process by which cancer cells spread to distant organs at an early stage of the disease, often before the primary tumor is clinically detectable. Experimental studies have demonstrated that Her2 promotes early dissemination of breast cancer by inhibiting th...
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| Format: | Article |
| Language: | English |
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BMC
2024-12-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-024-02000-2 |
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| author | Guanwen Wang Ping Wen Ting Xue Yuxin Huang Qing Shao Ningning Zhang Fanli Qu Jing Wang Nan Wang Xiaohua Zeng |
| author_facet | Guanwen Wang Ping Wen Ting Xue Yuxin Huang Qing Shao Ningning Zhang Fanli Qu Jing Wang Nan Wang Xiaohua Zeng |
| author_sort | Guanwen Wang |
| collection | DOAJ |
| description | Abstract Early dissemination refers to the process by which cancer cells spread to distant organs at an early stage of the disease, often before the primary tumor is clinically detectable. Experimental studies have demonstrated that Her2 promotes early dissemination of breast cancer by inhibiting the p38 signaling pathway. However, the precise mechanism by which Her2 suppresses the activation of p38 signaling in early-stage cancer cells (ECCs) remains unclear. Here, we report that MAP3K4, an upstream kinase of p38, is downregulated in Her2 + ductal carcinoma in situ (DCIS) cells and tissues, which is required for Her2-induced early dissemination of DCIS cells by regulating the activation of the p38 signaling cascade. Furthermore, Her2 suppresses the transcription of MAP3K4 by downregulating the expression of HOXB13, a crucial transcription factor contributing to MAP3K4 expression in DCIS cells. Together, these findings unveil a novel downstream regulatory mechanism through which Her2 inhibits the activation of p38 signaling and facilitates early dissemination of breast cancer, offering insights into the development of effective diagnostic methods and targeted therapies for inhibiting the early dissemination of Her2 + breast cancer. |
| format | Article |
| id | doaj-art-25accc8f4605486cb40ea6f16d6c1b1a |
| institution | DOAJ |
| issn | 1478-811X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-25accc8f4605486cb40ea6f16d6c1b1a2025-08-20T02:39:41ZengBMCCell Communication and Signaling1478-811X2024-12-0122111610.1186/s12964-024-02000-2Her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of MAP3K4Guanwen Wang0Ping Wen1Ting Xue2Yuxin Huang3Qing Shao4Ningning Zhang5Fanli Qu6Jing Wang7Nan Wang8Xiaohua Zeng9Department of Breast Cancer Center, Chongqing University Cancer HospitalSchool of Medicine, Chongqing University Cancer Hospital, Chongqing UniversitySchool of Medicine, Chongqing University Cancer Hospital, Chongqing UniversitySchool of Medicine, Chongqing University Cancer Hospital, Chongqing UniversityDepartment of Breast Cancer Center, Chongqing University Cancer HospitalDepartment of Breast Cancer Center, Chongqing University Cancer HospitalDepartment of Breast Cancer Center, Chongqing University Cancer HospitalInner Mongolia Autonomous Region People’s HospitalThe Second Surgical Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for CancerDepartment of Breast Cancer Center, Chongqing University Cancer HospitalAbstract Early dissemination refers to the process by which cancer cells spread to distant organs at an early stage of the disease, often before the primary tumor is clinically detectable. Experimental studies have demonstrated that Her2 promotes early dissemination of breast cancer by inhibiting the p38 signaling pathway. However, the precise mechanism by which Her2 suppresses the activation of p38 signaling in early-stage cancer cells (ECCs) remains unclear. Here, we report that MAP3K4, an upstream kinase of p38, is downregulated in Her2 + ductal carcinoma in situ (DCIS) cells and tissues, which is required for Her2-induced early dissemination of DCIS cells by regulating the activation of the p38 signaling cascade. Furthermore, Her2 suppresses the transcription of MAP3K4 by downregulating the expression of HOXB13, a crucial transcription factor contributing to MAP3K4 expression in DCIS cells. Together, these findings unveil a novel downstream regulatory mechanism through which Her2 inhibits the activation of p38 signaling and facilitates early dissemination of breast cancer, offering insights into the development of effective diagnostic methods and targeted therapies for inhibiting the early dissemination of Her2 + breast cancer.https://doi.org/10.1186/s12964-024-02000-2Breast cancerHer2Early disseminationp38MAP3K4HOXB13 |
| spellingShingle | Guanwen Wang Ping Wen Ting Xue Yuxin Huang Qing Shao Ningning Zhang Fanli Qu Jing Wang Nan Wang Xiaohua Zeng Her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of MAP3K4 Cell Communication and Signaling Breast cancer Her2 Early dissemination p38 MAP3K4 HOXB13 |
| title | Her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of MAP3K4 |
| title_full | Her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of MAP3K4 |
| title_fullStr | Her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of MAP3K4 |
| title_full_unstemmed | Her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of MAP3K4 |
| title_short | Her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of MAP3K4 |
| title_sort | her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of map3k4 |
| topic | Breast cancer Her2 Early dissemination p38 MAP3K4 HOXB13 |
| url | https://doi.org/10.1186/s12964-024-02000-2 |
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