Abstract 4957: Keratin 13 drives the dissemination of bone and brain metastases of human prostate and breast cancer cells

Abstract

Abstract Introduction and Objective: Bone and brain metastases are prevalent in human prostate and breast cancer patients. Keratin 13 (KRT13), a member of the intermediate filament proteins and an epithelial stem cell differentiation marker, induces cancer cell migration and progression toward increased malignant state. The objectives of this study are: 1) to determine KRT13 expression in human prostate and breast cancer and its clinical correlation; 2) to determine the functional cell signaling role of KRT13 in prostate and breast cancer cells using gene transfer technology. Methods and Results: We evaluated KRT13 protein expression in primary prostate cancer tissues from 44 cases with well-documented overall survival by quantitative quantum dot immuno-labelling. We found that KRT13 expression in primary prostate cancer correlated with patient overall survival and bone metastasis (p<0.05). We next evaluated KRT13 protein expression in 36 prostate and 58 breast cancer tissue specimens by immunohistochesmistry (IHC) and found that KRT13 is overexpressed in breast cancer bone (5/8) and brain (7/10) metastases and prostate cancer bone (6/12) metastasis specimens (p<0.05). KRT13 expression in primary prostate and breast cancer specimens is associated with decreased patient overall survival based on our data as well as publicly available Oncomine gene expression datasets. To elucidate the mechanisms by which KRT13 promotes cancer invasion, migration and metastasis, we genetically overexpressed KRT13 in human prostate CWR22 Rv1 and LNCaP, and human breast MCF7 and MCF10A cells, with respectively high or low malignant potential. KRT13-overexpressing prostate and breast cancer cells increase differential expression of genes associated with epithelial to mesenchymal transition (EMT; E-Cadherin and Vimentin), stemness (Nanog), neuromimicry (Chromagranin A and Synaptophysin), osteomimicry (RANKL) related genes as analyzed by qRT-PCR, western blot, and IHC. KRT13 also promotes increased cancer cell proliferation, migration and invasion in vitro, and bone and brain metastases in vivo. Conclusion: These results suggest that KRT13 drives prostate and breast cancer bone and brain metastases via osteomimicry and neuromimicry associated genes resulting in downstream cell signaling network convergence between EMT, stemness, cell growth, and survival pathways. Funded in part by NCI-P01-CA098912 Citation Format: Lijuan Yin, Qinlong Li, Jen-Ming Huang, Michael Lewis, Isla P. Garraway, Quanlin Li, Hong Bu, Leland W. K Chung, Haiyen E. Zhau. Keratin 13 drives the dissemination of bone and brain metastases of human prostate and breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4957.