BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by advanced disease stage and poor prognosis. Moreover, due to the lack of therapeutic markers, TNBC patients can't benefit fully from currently available targeted therapies. METHODS: To fully understand the molecular basis of TNBC, we used gene set enrichment analysis (GSEA) to screen out the most altered functional module in TNBC, from publicly available microarray data and studied the association of the candidate gene with TNBC development. RESULTS: We found that the proteasome was significantly activated in TNBC. As compared with other breast cancer subtypes and normal tissue, proteasome subunit beta 5 (PSMB5), the key regulator of proteasome function, was overexpressed in TNBC tissue and predictive of poor prognosis. Moreover, we also found that PSMB5 knockdown induced TNBC apoptosis and significantly enhanced cancer cell sensitivity to the chemotherapeutic agents bortezomib and paclitaxel. CONCLUSIONS: Our results suggest a potential role for PSMB5 as a biomarker and therapeutic target for TNBC.
BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by advanced disease stage and poor prognosis. Moreover, due to the lack of therapeutic markers, TNBC patients can't benefit fully from currently available targeted therapies. METHODS: To fully understand the molecular basis of TNBC, we used gene set enrichment analysis (GSEA) to screen out the most altered functional module in TNBC, from publicly available microarray data and studied the association of the candidate gene with TNBC development. RESULTS: We found that the proteasome was significantly activated in TNBC. As compared with other breast cancer subtypes and normal tissue, proteasome subunit beta 5 (PSMB5), the key regulator of proteasome function, was overexpressed in TNBC tissue and predictive of poor prognosis. Moreover, we also found that PSMB5 knockdown induced TNBC apoptosis and significantly enhanced cancer cell sensitivity to the chemotherapeutic agents bortezomib and paclitaxel. CONCLUSIONS: Our results suggest a potential role for PSMB5 as a biomarker and therapeutic target for TNBC.
Entities:
Keywords:
Bortezomib; Paclitaxel; Proteasome subunit beta 5 (PSMB5); TNBC; Triple-negative breast cancer
Authors: Jun Fang; Wen Hao Ji; Fang Zheng Wang; Tie Ming Xie; Lei Wang; Zhen Fu Fu; Zhun Wang; Feng Qin Yan; Qi Liang Shen; Zhi Min Ye Journal: J Cancer Date: 2021-03-05 Impact factor: 4.207
Authors: Sourav Banerjee; Tiantian Wei; Jue Wang; Jenna J Lee; Haydee L Gutierrez; Owen Chapman; Sandra E Wiley; Joshua E Mayfield; Vasudha Tandon; Edwin F Juarez; Lukas Chavez; Ruqi Liang; Robert L Sah; Caitlin Costello; Jill P Mesirov; Laureano de la Vega; Kimberly L Cooper; Jack E Dixon; Junyu Xiao; Xiaoguang Lei Journal: Proc Natl Acad Sci U S A Date: 2019-11-21 Impact factor: 11.205