SMC1A is associated with radioresistance in prostate cancer and acts by regulating epithelial-mesenchymal transition and cancer stem-like properties.
Prostate cancer is one of the most commonly diagnosed cancers and a pressing health challenge in men worldwide. Radiation therapy (RT) is widely considered a standard therapy for advanced as well as localized prostate cancer. Although this primary therapy is associated with high cancer control rates, up to one-third of patients undergoing radiation therapy becomes radio-resistant and/or has tumor-relapse/recurrence. Therefore, focus on new molecular targets and pathways is essential to develop novel radio-sensitizing agents for the effective and safe treatment of prostate cancer. Here, we describe functional studies that were performed to investigate the role of structural maintenance of chromosome-1 (SMC1A) in radioresistance of metastatic prostate cancer cells. Short hairpin RNA (shRNA) was used to suppress SMC1A in metastatic castration-resistant prostate cancer cells, DU145 and PC3. Clonogenic survival assays, Western blot, RT-PCR, and γ-H2AX staining were used to assess the effect of SMC1A knockdown on radiation sensitivity of these prostate cancer cells. We demonstrate that SMC1A is overexpressed in human prostate tumors compared to the normal adjacent tissue. SMC1A knockdown limits the clonogenic potential, epithelial-mesenchymal transition (EMT), and cancer stem-like cell (CSC) properties of DU145 and PC3 cells and enhanced efficacy of RT in these cells. Targeted inhibition of SMC1A not only plays a critical role in overcoming radio-resistance in prostate cancer cells, but also suppresses self-renewal and the tumor-propagating potential of x-irradiated cancer cells. We propose that SMC1A could be a potential molecular target for the development of novel radio-sensitizing therapeutic agents for management of radio-resistant metastatic prostate cancer.
['Yadav|Sushma|S|0000-0003-1716-9446', 'Kowolik|Claudia M|CM|', 'Lin|Min|M|', 'Zuro|Darren|D|', 'Hui|Susanta K|SK|', 'Riggs|Arthur D|AD|', 'Horne|David A|DA|']
D017209:Apoptosis D014408:Biomarkers, Tumor D018797:Cell Cycle Proteins D002465:Cell Movement D049109:Cell Proliferation D002868:Chromosomal Proteins, Non-Histone D058750:Epithelial-Mesenchymal Transition D005500:Follow-Up Studies D005720:Gamma Rays D006801:Humans D008297:Male D009362:Neoplasm Metastasis D009364:Neoplasm Recurrence, Local D014411:Neoplastic Stem Cells D011379:Prognosis D011471:Prostatic Neoplasms D011836:Radiation Tolerance D014407:Tumor Cells, Cultured
structural maintenance of chromosome-1 cancer stem-like cells DNA-damage repair epithelial to mesenchymal transition metastatic castration resistant prostate cancer radiation-resistance reactive oxygen species