Project description:To study the expression of SIPA1 in patients with metastatic triple-negative breast cancer, we obtained a subcutaneous metastatic sample from a patient with stage III triple-negative breast cancer and performed single-cell transcriptome sequencing
Project description:SIPA1 is a potential transcriptional modulator of tumor metastasis and recurrence. Here we showed that the breast cancer patients with higher SIPA1 expression have a higher relapse rate and worse prognosis, especially for triple-negative breast cancer (TNBC) patients. Moreover, SIPA1 expression was found positively correlated with relapse of breast cancer patients receiving adjuvant chemotherapy. In a TNBC cell line MDA-MB-231, we identified the possible tumorigenesis and metastasis processes regulated by SIPA1, and demonstrated that SIPA1 promoted cancer stem-like feature to form tumourspheres. Tumoursphere-formed MDA-MB-231 cells were shown to be resistant to epirubicin. Then we confirmed that SIPA1 could particularly activate the CD44 promoter and upregulate CD44 expression. Furthermore, SIPA1 could promote ABCB1 expression and strengthen chemoresistance of MDA-MB-231 cells to epirubicin. In conclusion, SIPA1 is a risk factor for highly-relapse in TNBC patients and a transcriptional regulator to maintain cancer stem-like features and promote chemoresistance in breast cancer cells.
Project description:To further study the regulation of SIPA1 on cells, the transcriptome sequencing on BT549 cells, BT549/shSIPA1 cells and si-dDBR cells were performed. We then performed gene expression profiling analysis using data obtained from RNA-seq of BT549 cells, BT549/shSIPA1 cells and si-dDBR cells to find the genes regulated by SIPA1.
Project description:Mass spectrometry profiling of orthotopically transplanted breast cancer patient-derived xenograft (PDX) tumors prior to chemotherapy treatment.
Project description:Breast cancer is a heterogenous disease that is difficult to model in vitro. Frozen primary breast cancers were decellularised to generate patient-derived scaffolds which are used to model 3D growth for cancer cell lines. The cell-free cancer microenvironments in the patient-derived scaffolds influence breast cancer cell line phenotypes and enrich for cells with cancer stem cell characteristics. Growth in patient-derived scaffold cultures also influenced the expression of epithelial-to-mesenchymal transition-related genes, and several gene expression changes in the model could be associated to clinical parameters of the original tumors and corresponding patients. Previous studies also demonstrated that the relative protein composition in the cell-free cancers were related to tumor grade and proliferation in cancer cells, suggesting that the relative proteomic composition varies between individual microenvironments. Therefore, we decellularised a larger breast cancer cohort to better characterize the cell-free microenvironments and potentially link to clinical features of the tumors and patients, which could be used to identify novel processes and targets that could be used to better model the disease or targeted in drug discovery.