TWIST modulates prostate cancer cell-mediated bone cell activity and is upregulated by osteogenic induction
| Autor: | Xianghong Wang, WK Kwok, Ying-Ying Chu, Kwok Wah Chan, Hiu-Fung Yuen, Chee-Wai Chua, Ka-Kui Chan, Yuen-Piu Chan, Yong-Chuan Wong |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty animal structures Bone Neoplasms Core Binding Factor Alpha 1 Subunit Bone and Bones Cell Line Bone remodeling Mice Prostate cancer Calcification Physiologic Genes Reporter Osteogenesis Osteoclast Cell Line Tumor Internal medicine Bone cell medicine Animals Humans RNA Small Interfering DNA Primers Osteoblasts business.industry Twist-Related Protein 1 Nuclear Proteins Prostatic Neoplasms Cancer Bone metastasis Osteoblast 3T3 Cells General Medicine Alkaline Phosphatase medicine.disease Up-Regulation RUNX2 medicine.anatomical_structure Endocrinology Cancer research business Plasmids |
| Zdroj: | Carcinogenesis. 29:1509-1518 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgn105 |
| Popis: | TWIST, a helix-loop-helix transcription factor, is highly expressed in many types of human cancer. We have previously found that TWIST confers prostate cancer cells with an enhanced metastatic potential through promoting epithelial-mesenchymal transition (EMT) and a high TWIST expression in human prostate cancer is associated with an increased metastatic potential. The predilection of prostate cancer cells to metastasize to bone may be due to two interplaying mechanisms (i) by increasing the rate of bone remodeling and (ii) by undergoing osteomimicry. We further studied the role of TWIST in promoting prostate cancer to bone metastasis. TWIST expression in PC3, a metastatic prostate cancer cell line, was silenced by small interfering RNA and we found that conditioned medium from PC3 with lower TWIST expression had a lower activity on stimulating osteoclast differentiation and higher activity on stimulating osteoblast mineralization. In addition, we found that these effects were, at least partly, associated with TWIST-induced expression of dickkopf homolog 1 (DKK-1), a factor that promotes osteolytic metastasis. We also examined TWIST and RUNX2 expressions during osteogenic induction of an organ-confined prostate cancer cell, 22Rv1. We observed increased TWIST and RUNX2 expressions upon osteogenic induction and downregulation of TWIST through short hairpin RNA reduced the induction level of RUNX2. In summary, our results suggest that, in addition to EMT, TWIST may also promote prostate cancer to bone metastasis by modulating prostate cancer cell-mediated bone remodeling via regulating the expression of a secretory factor, DKK-1, and enhancing osteomimicry of prostate cancer cells, probably, via RUNX2. |
| Databáze: | OpenAIRE |
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