Accession Number:

ADA551370

Title:

Targeted Analysis of KLF6/KLF6-SV1 Regulating Pathways in Prostate Cancer Development and Metastasis

Descriptive Note:

Annual summary rept. 15 Aug 2009-14 Aug 2011

Corporate Author:

MOUNT SINAI SCHOOL OF MEDICINE NEW YORK

Personal Author(s):

Report Date:

2011-09-01

Pagination or Media Count:

33.0

Abstract:

KLF6 is a member of the Kruppel-like transcription factor family which was first identified as a tumor suppressor gene frequently inactivated in prostate cancer PCa. A single germline SNP increases PCa risk and KLF6 gene alternative splicing to produce KLF6-SV1, which promotes tumor cell growth and metastasis. Since their original discoveries, many downstream cancer-relevant targets have been described as regulated by KLF6 and KLF6-SV1. However, less is known about the molecular pathways that regulate the function of these proteins. Therefore, the main purpose of this project was to identify the molecular pathways by which KLF6KLF6-SV1 are involved in the initiation, progression and metastasis of PCa. We have been highly successful in moving the project forward during the last two years. Indeed, our recent publication describes the work performed as part of Specfic Aim 1 Appendix. The paper describes our successful identification and characterization of the nucleo-cytoplasmic localization domains that regulate KLF6KLF6-SV1 shuttling, protein stability and tumor suppressor function. The manuscript that acknowledges the support of this post-doctoral training award was published in PLoS ONE in 2009. As a more translational outcome of this Aim, these results allowed us to establish a collaboration with a biopharmaceutical company to test nuclear export inhibitors as potential drugs for the treatment of prostate cancer. Work is now ongoing. In addition to this, we were also requested to provide a research editorial on the KLF family and their role in human cancer, which was published soon after the start of this initial funding period. A copy of the manuscript, The Kr ppel traffic report cooperative signals direct KLF8 nuclear transport , Rodr guez E, Martignetti JA. Cell Res. 2009 Sep19 91041-3, is included in the Appendix. Beyond this, we have also started developing the constructs necessary for completion of the second part of Aim1 and Aim2.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE