STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancer
In the clinic, anti-tumor angiogenesis is commonly employed for treating recurrent, metastatic, drug-resistant triple-negative, and advanced breast cancer. Our previous research revealed that the deubiquitinase STAMBPL1 enhances the stability of MKP-1, thereby promoting cisplatin resistance in breas...
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| Format: | Article |
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eLife Sciences Publications Ltd
2025-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/102433 |
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| author | Huan Fang Huichun Liang Chuanyu Yang Dewei Jiang Qianmei Luo Wen-Ming Cao Huifeng Zhang Ceshi Chen |
| author_facet | Huan Fang Huichun Liang Chuanyu Yang Dewei Jiang Qianmei Luo Wen-Ming Cao Huifeng Zhang Ceshi Chen |
| author_sort | Huan Fang |
| collection | DOAJ |
| description | In the clinic, anti-tumor angiogenesis is commonly employed for treating recurrent, metastatic, drug-resistant triple-negative, and advanced breast cancer. Our previous research revealed that the deubiquitinase STAMBPL1 enhances the stability of MKP-1, thereby promoting cisplatin resistance in breast cancer. In this study, we discovered that STAMBPL1 could upregulate the expression of the hypoxia-inducible factor HIF1α in breast cancer cells. Therefore, we investigated whether STAMBPL1 promotes tumor angiogenesis. We demonstrated that STAMBPL1 increased HIF1A transcription in a non-enzymatic manner, thereby activating the HIF1α/VEGFA signaling pathway to facilitate triple-negative breast cancer angiogenesis. Through RNA-seq analysis, we identified the transcription factor GRHL3 as a downstream target of STAMBPL1 that is responsible for mediating HIF1A transcription. Furthermore, we discovered that STAMBPL1 regulates GRHL3 transcription by interacting with the transcription factor FOXO1. These findings shed light on the role and mechanism of STAMBPL1 in the pathogenesis of breast cancer, offering novel targets and avenues for the treatment of triple-negative and advanced breast cancer. |
| format | Article |
| id | doaj-art-d8b273aa39604eb1b320d5db2d32cb4e |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-d8b273aa39604eb1b320d5db2d32cb4e2025-08-20T02:16:55ZengeLife Sciences Publications LtdeLife2050-084X2025-04-011310.7554/eLife.102433STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancerHuan Fang0https://orcid.org/0009-0003-0489-5796Huichun Liang1https://orcid.org/0000-0002-9157-3087Chuanyu Yang2Dewei Jiang3Qianmei Luo4Wen-Ming Cao5Huifeng Zhang6Ceshi Chen7https://orcid.org/0000-0001-6398-3516Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Kunming College of Life Sciences, University of Chinese Academy of Sciences, Kunming, ChinaKunming Institute of Zoology, Chinese Academy of Sciences, Kunming, ChinaKunming Institute of Zoology, Chinese Academy of Sciences, Kunming, ChinaKunming Institute of Zoology, Chinese Academy of Sciences, Kunming, ChinaKunming Institute of Zoology, Chinese Academy of Sciences, Kunming, ChinaThe Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, ChinaDepartment of Pharmacy, the First People’s Hospital of Yunnan Province/the Affiliated Hospital of Kunming University of Science and Technology, Kunming, ChinaKunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Academy of Biomedical Engineering, Kunming Medical University, Kunming, China; The Third Affiliated Hospital, Kunming Medical University, Kunming, ChinaIn the clinic, anti-tumor angiogenesis is commonly employed for treating recurrent, metastatic, drug-resistant triple-negative, and advanced breast cancer. Our previous research revealed that the deubiquitinase STAMBPL1 enhances the stability of MKP-1, thereby promoting cisplatin resistance in breast cancer. In this study, we discovered that STAMBPL1 could upregulate the expression of the hypoxia-inducible factor HIF1α in breast cancer cells. Therefore, we investigated whether STAMBPL1 promotes tumor angiogenesis. We demonstrated that STAMBPL1 increased HIF1A transcription in a non-enzymatic manner, thereby activating the HIF1α/VEGFA signaling pathway to facilitate triple-negative breast cancer angiogenesis. Through RNA-seq analysis, we identified the transcription factor GRHL3 as a downstream target of STAMBPL1 that is responsible for mediating HIF1A transcription. Furthermore, we discovered that STAMBPL1 regulates GRHL3 transcription by interacting with the transcription factor FOXO1. These findings shed light on the role and mechanism of STAMBPL1 in the pathogenesis of breast cancer, offering novel targets and avenues for the treatment of triple-negative and advanced breast cancer.https://elifesciences.org/articles/102433triple-negative breast cancertumor angiogenesisSTAMBPL1FOXO1GRHL3HIF1α |
| spellingShingle | Huan Fang Huichun Liang Chuanyu Yang Dewei Jiang Qianmei Luo Wen-Ming Cao Huifeng Zhang Ceshi Chen STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancer eLife triple-negative breast cancer tumor angiogenesis STAMBPL1 FOXO1 GRHL3 HIF1α |
| title | STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancer |
| title_full | STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancer |
| title_fullStr | STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancer |
| title_full_unstemmed | STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancer |
| title_short | STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancer |
| title_sort | stambpl1 activates the grhl3 hif1a vegfa axis through interaction with foxo1 to promote angiogenesis in triple negative breast cancer |
| topic | triple-negative breast cancer tumor angiogenesis STAMBPL1 FOXO1 GRHL3 HIF1α |
| url | https://elifesciences.org/articles/102433 |
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