Targeting of HBP1/TIMP3 axis as a novel strategy against breast cancer

Abstract

Malignant proliferation and metastasis are the main causes of breast cancer death. The transcription factor high mobility group (HMG) box-containing protein 1 (HBP1) is an important tumor suppressor whose deletion or mutation is closely related to the appearance of tumors. Here, we investigated the role of HBP1 in breast cancer suppression. HBP1 enhances the activity of the tissue inhibitors of metalloproteinases 3 (TIMP3) promoter, thereby increasing protein and mRNA levels of TIMP3. TIMP3 increases the phosphatase and tensin homolog (PTEN) protein level by inhibiting its degradation and acts as a metalloproteinase inhibitor to inhibit the protein levels of MMP2/9. In this study, we demonstrated that the HBP1/TIMP3 axis plays a crucial role in inhibiting the tumorigenesis of breast cancer. HBP1 deletion interferes with the regulation of the axis and induces the occurrence and malignant progression of breast cancer. In addition, the HBP1/TIMP3 axis promotes the sensitivity of breast cancer to radiation therapy and hormone therapy. Our study opens new perspectives on the treatment and prognosis of breast cancer.

Keywords: 7,12-Dimethylbenz[a]anthracene (DMBA, PubChem CID: 6001); Breast cancer; Disodium phosphate dodecahydrate (PubChem CID: 61456); Epigallocatechin Gallate (PubChem CID: 65064); Ethylenediaminetetraacetic acid (PubChem CID: 6049); HBP1; MMP2/9; PTEN; Potassium Chloride (PubChem CID:4873); Potassium dihydrogen phosphate (PubChem CID: 516951); Radiotherapy; Sodium Chloride (PubChem CID: 5234); Sodium dodecyl sulfate (PubChem CID: 3423265); TIMP3; Tamoxifen (PubChem CID: 2733526); Tromethamine (PubChem CID: 6503).