Academic Journal
STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancer
| Title: | STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancer |
|---|---|
| Authors: | Huan Fang, Huichun Liang, Chuanyu Yang, Dewei Jiang, Qianmei Luo, Wen-Ming Cao, Huifeng Zhang, Ceshi Chen |
| Source: | eLife, Vol 13 (2025) |
| Publisher Information: | eLife Sciences Publications Ltd, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | triple-negative breast cancer, tumor angiogenesis, STAMBPL1, FOXO1, GRHL3, HIF1α, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/102433; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.102433 |
| Access URL: | https://doaj.org/article/d8b273aa39604eb1b320d5db2d32cb4e |
| Accession Number: | edsdoj.8b273aa39604eb1b320d5db2d32cb4e |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
|---|---|
| DOI: | 10.7554/eLife.102433 |
| Published in: | eLife |
| Language: | English |