ASC-J9® suppresses prostate cancer cell proliferation and invasion via altering the ATF3-PTK2 signaling
Abstract Background Early studies indicated that ASC-J9®, an androgen receptor (AR) degradation enhancer, could suppress the prostate cancer (PCa) progression. Here we found ASC-J9® could also suppress the PCa progression via an AR-independent mechanism, which might involve modulating the tumor supp...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-020-01760-2 |
| _version_ | 1818970850068529152 |
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| author | Hao Tian Fu-ju Chou Jing Tian Yong Zhang Bosen You Chi-Ping Huang Shuyuan Yeh Yuanjie Niu Chawnshang Chang |
| author_facet | Hao Tian Fu-ju Chou Jing Tian Yong Zhang Bosen You Chi-Ping Huang Shuyuan Yeh Yuanjie Niu Chawnshang Chang |
| author_sort | Hao Tian |
| collection | DOAJ |
| description | Abstract Background Early studies indicated that ASC-J9®, an androgen receptor (AR) degradation enhancer, could suppress the prostate cancer (PCa) progression. Here we found ASC-J9® could also suppress the PCa progression via an AR-independent mechanism, which might involve modulating the tumor suppressor ATF3 expression. Methods The lentiviral system was used to modify gene expression in C4–2, CWR22Rv1 and PC-3 cells. Western blot and Immunohistochemistry were used to detect protein expression. MTT and Transwell assays were used to test the proliferation and invasion ability. Results ASC-J9® can suppress PCa cell proliferation and invasion in both PCa C4–2 and CWR22Rv1 cells via altering the ATF3 expression. Further mechanistic studies reveal that ASC-J9® can increase the ATF3 expression via decreasing Glutamate-cysteine ligase catalytic (GCLC) subunit expression, which can then lead to decrease the PTK2 expression. Human clinical studies further linked the ATF3 expression to the PCa progression. Preclinical studies using in vivo mouse model also proved ASC-J9® could suppress AR-independent PCa cell invasion, which could be reversed after suppressing ATF3. Conclusions ASC-J9® can function via altering ATF3/PTK2 signaling to suppress the PCa progression in an AR-independent manner. |
| first_indexed | 2024-12-20T14:43:01Z |
| format | Article |
| id | doaj.art-10a90f593d664ad88f99c8b92059e65d |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-20T14:43:01Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-10a90f593d664ad88f99c8b92059e65d2022-12-21T19:37:12ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-01-0140111210.1186/s13046-020-01760-2ASC-J9® suppresses prostate cancer cell proliferation and invasion via altering the ATF3-PTK2 signalingHao Tian0Fu-ju Chou1Jing Tian2Yong Zhang3Bosen You4Chi-Ping Huang5Shuyuan Yeh6Yuanjie Niu7Chawnshang Chang8Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin Medical UniversityGeorge Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical CenterDepartment of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin Medical UniversityDepartment of Urology, the Second Hospital of Hebei Medical UniversityGeorge Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical CenterSex Hormone Research Center, Department of Urology, China Medical UniversityGeorge Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical CenterDepartment of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin Medical UniversityGeorge Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical CenterAbstract Background Early studies indicated that ASC-J9®, an androgen receptor (AR) degradation enhancer, could suppress the prostate cancer (PCa) progression. Here we found ASC-J9® could also suppress the PCa progression via an AR-independent mechanism, which might involve modulating the tumor suppressor ATF3 expression. Methods The lentiviral system was used to modify gene expression in C4–2, CWR22Rv1 and PC-3 cells. Western blot and Immunohistochemistry were used to detect protein expression. MTT and Transwell assays were used to test the proliferation and invasion ability. Results ASC-J9® can suppress PCa cell proliferation and invasion in both PCa C4–2 and CWR22Rv1 cells via altering the ATF3 expression. Further mechanistic studies reveal that ASC-J9® can increase the ATF3 expression via decreasing Glutamate-cysteine ligase catalytic (GCLC) subunit expression, which can then lead to decrease the PTK2 expression. Human clinical studies further linked the ATF3 expression to the PCa progression. Preclinical studies using in vivo mouse model also proved ASC-J9® could suppress AR-independent PCa cell invasion, which could be reversed after suppressing ATF3. Conclusions ASC-J9® can function via altering ATF3/PTK2 signaling to suppress the PCa progression in an AR-independent manner.https://doi.org/10.1186/s13046-020-01760-2ASC-J9®ATF3Prostate cancerATF3 response elementPTK2 |
| spellingShingle | Hao Tian Fu-ju Chou Jing Tian Yong Zhang Bosen You Chi-Ping Huang Shuyuan Yeh Yuanjie Niu Chawnshang Chang ASC-J9® suppresses prostate cancer cell proliferation and invasion via altering the ATF3-PTK2 signaling Journal of Experimental & Clinical Cancer Research ASC-J9® ATF3 Prostate cancer ATF3 response element PTK2 |
| title | ASC-J9® suppresses prostate cancer cell proliferation and invasion via altering the ATF3-PTK2 signaling |
| title_full | ASC-J9® suppresses prostate cancer cell proliferation and invasion via altering the ATF3-PTK2 signaling |
| title_fullStr | ASC-J9® suppresses prostate cancer cell proliferation and invasion via altering the ATF3-PTK2 signaling |
| title_full_unstemmed | ASC-J9® suppresses prostate cancer cell proliferation and invasion via altering the ATF3-PTK2 signaling |
| title_short | ASC-J9® suppresses prostate cancer cell proliferation and invasion via altering the ATF3-PTK2 signaling |
| title_sort | asc j9 r suppresses prostate cancer cell proliferation and invasion via altering the atf3 ptk2 signaling |
| topic | ASC-J9® ATF3 Prostate cancer ATF3 response element PTK2 |
| url | https://doi.org/10.1186/s13046-020-01760-2 |
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