Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA
Abstract Triple-negative breast cancer (TNBC) represents the most challenging subtype of breast cancer. Studies have implicated an upregulation of lipid synthesis pathways in the initiation and progression of TNBC. Targeting lipid synthesis pathways may be a promising therapeutic strategy for TNBC....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-023-01749-7 |
| _version_ | 1797387997849583616 |
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| author | Pan Hu Peiyi Zhou Tieyun Sun Dingkang Liu Jun Yin Lubin Liu |
| author_facet | Pan Hu Peiyi Zhou Tieyun Sun Dingkang Liu Jun Yin Lubin Liu |
| author_sort | Pan Hu |
| collection | DOAJ |
| description | Abstract Triple-negative breast cancer (TNBC) represents the most challenging subtype of breast cancer. Studies have implicated an upregulation of lipid synthesis pathways in the initiation and progression of TNBC. Targeting lipid synthesis pathways may be a promising therapeutic strategy for TNBC. Our previous study developed a therapeutic protein PAK with passive targeting and inhibiting tumor proliferation. In this study, we further substantiate the efficacy of PAK in TNBC. Transcriptome sequencing analysis revealed PAK-mediated downregulation of genes involved in fatty acid synthesis, including key genes like SREBP-1, FASN, and SCD1. RNA immunoprecipitation experiments demonstrated a significant binding affinity of PAK to SREBP-1 mRNA, facilitating its degradation process. Both in vitro and in vivo models, PAK hampered TNBC progression by downregulating lipid synthesis pathways. In conclusion, this study emphasizes that PAK inhibits the progression of TNBC by binding to and degrading SREBP-1 mRNA, revealing a new strategy for regulating lipid synthesis in the intervention of TNBC and its therapeutic significance. |
| first_indexed | 2024-03-08T22:34:18Z |
| format | Article |
| id | doaj.art-66cc58ac59734cdba1326fcba9ee4439 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-03-08T22:34:18Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-66cc58ac59734cdba1326fcba9ee44392023-12-17T12:34:08ZengBMCBreast Cancer Research1465-542X2023-12-0125111210.1186/s13058-023-01749-7Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNAPan Hu0Peiyi Zhou1Tieyun Sun2Dingkang Liu3Jun Yin4Lubin Liu5Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical UniversityDepartment of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical UniversityDepartment of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical UniversityJiangsu Key Laboratory of Druggability of Biopharmaceuticals and State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical UniversityJiangsu Key Laboratory of Druggability of Biopharmaceuticals and State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical UniversityDepartment of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical UniversityAbstract Triple-negative breast cancer (TNBC) represents the most challenging subtype of breast cancer. Studies have implicated an upregulation of lipid synthesis pathways in the initiation and progression of TNBC. Targeting lipid synthesis pathways may be a promising therapeutic strategy for TNBC. Our previous study developed a therapeutic protein PAK with passive targeting and inhibiting tumor proliferation. In this study, we further substantiate the efficacy of PAK in TNBC. Transcriptome sequencing analysis revealed PAK-mediated downregulation of genes involved in fatty acid synthesis, including key genes like SREBP-1, FASN, and SCD1. RNA immunoprecipitation experiments demonstrated a significant binding affinity of PAK to SREBP-1 mRNA, facilitating its degradation process. Both in vitro and in vivo models, PAK hampered TNBC progression by downregulating lipid synthesis pathways. In conclusion, this study emphasizes that PAK inhibits the progression of TNBC by binding to and degrading SREBP-1 mRNA, revealing a new strategy for regulating lipid synthesis in the intervention of TNBC and its therapeutic significance.https://doi.org/10.1186/s13058-023-01749-7Therapeutic proteinLipogenesisFatty acidSREBP-1Triple negative breast cancer |
| spellingShingle | Pan Hu Peiyi Zhou Tieyun Sun Dingkang Liu Jun Yin Lubin Liu Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA Breast Cancer Research Therapeutic protein Lipogenesis Fatty acid SREBP-1 Triple negative breast cancer |
| title | Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA |
| title_full | Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA |
| title_fullStr | Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA |
| title_full_unstemmed | Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA |
| title_short | Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA |
| title_sort | therapeutic protein pak restrains the progression of triple negative breast cancer through degrading srebp 1 mrna |
| topic | Therapeutic protein Lipogenesis Fatty acid SREBP-1 Triple negative breast cancer |
| url | https://doi.org/10.1186/s13058-023-01749-7 |
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