Metastatic, hormone independent prostate cancer (CAP) is incurable. The goal of this multidisciplinary Program Project is to elucidate the signal transduction mechanisms that underlie the stepwise events associated with progression of CaP from a localized and androgen sensitive tumor to a disseminated and androgen independent one. The Program brings together productive and experienced investigators with complementary expertise relevant to the stated goal of the Program and backgrounds in signal transduction (J. T. Parsons, S. J. Parsons, Schwartz, Weber), nuclear receptor biology (Paschal), bone biology (Chirgwin, Guise) and basic and clinical prostate cancer metastasis research (Theodorescu). In Project 1, D. Theodorescu and J. T. Parsons propose to evaluate the roles of VEGF and FAK in determining the tropism of CaP metastasis to bone; Project 2, T. Guise and J. Chirgwin will study the impact of adrenomedullin in bone metastasis; Project 3, M. Weber studies Ras-mediated signaling cascades as they affect ligand independent androgen receptor activity; Project 4, B. Paschal proposes to study the relationship between androgen receptor activation and the control of its nuclear localization; Project 5, S. J. Parsons studies the regulation of neuroendocrine cell growth within advanced prostate cancers and the impact of such cells on overall tumor dependence on androgen; Project 6, M. Schwartz works on novel ways of exploiting synergies between inhibition of cell adhesion signaling and chemotherapy as a way to enhance the therapeutic index of the latter in androgen independent CaP. This interactive Program relies heavily on synergistic technical and scientific expertise from all investigators. The productivity of individual Projects is catalyzed by highly integrated Cores led by H. Frierson, an expert surgical pathologist who specializes in CaP, T. Guise who has extensive experience in bone histology and histomorphometry, J. T. Parsons who is highly experienced at live cell microscopy, M. Conaway an expert biostatistician and D. Theodorescu who is familiar with the biology of prostate cancer and the xenograft models used in prostate cancer research. Together, these Projects integrate diverse skills and expertise to focus on areas fundamental to our understanding tumor progression in CaP, with the objective of accelerating progress in developing a cure for this devastating disease.
| Kuscu, Canan; Kumar, Pankaj; Kiran, Manjari et al. (2018) tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner. RNA 24:1093-1105 |
| Hao, Yi; Bjerke, Glen A; Pietrzak, Karolina et al. (2018) TGF? signaling limits lineage plasticity in prostate cancer. PLoS Genet 14:e1007409 |
| Yang, Chun-Song; Melhuish, Tiffany A; Spencer, Adam et al. (2017) The protein kinase C super-family member PKN is regulated by mTOR and influences differentiation during prostate cancer progression. Prostate 77:1452-1467 |
| Agarwal, Neeraj; Dancik, Garrett M; Goodspeed, Andrew et al. (2016) GON4L Drives Cancer Growth through a YY1-Androgen Receptor-CD24 Axis. Cancer Res 76:5175-85 |
| Reon, Brian J; Dutta, Anindya (2016) Biological Processes Discovered by High-Throughput Sequencing. Am J Pathol 186:722-32 |
| Kumar, Pankaj; Kuscu, Canan; Dutta, Anindya (2016) Biogenesis and Function of Transfer RNA-Related Fragments (tRFs). Trends Biochem Sci 41:679-689 |
| Sakurai, Kouhei; Reon, Brian J; Anaya, Jordan et al. (2015) The lncRNA DRAIC/PCAT29 Locus Constitutes a Tumor-Suppressive Nexus. Mol Cancer Res 13:828-38 |
| Dillon, Laura W; Kumar, Pankaj; Shibata, Yoshiyuki et al. (2015) Production of Extrachromosomal MicroDNAs Is Linked to Mismatch Repair Pathways and Transcriptional Activity. Cell Rep 11:1749-59 |
| Kumar, Pankaj; Mudunuri, Suresh B; Anaya, Jordan et al. (2015) tRFdb: a database for transfer RNA fragments. Nucleic Acids Res 43:D141-5 |
| Earl, Julie; Rico, Daniel; Carrillo-de-Santa-Pau, Enrique et al. (2015) The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies. BMC Genomics 16:403 |
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