PL 29. KLF4 - A Metastasis Suppressor Gene for Prostate Cancer

Prostate cancer is one of the most commonly diagnosed cancers and a leading cause of cancer deaths in men. Progression of prostate cancer to invasive and metastatic disease, known as advanced prostate cancer, occurs in over 50% patients and represents the most deadly step that threatens the life of patients and cannot be cured by existing therapies. Our current understanding of the molecular events governing prostate cancer metastasis is very limited. Clinically, there is no reliable biomarker that can predict which patients are at risk of developing metastasis and there is no effective treatment that can eradicate metastatic prostate cancer cells. KLF4/GKLF (gutenriched Krüpple-like factor) is a member of the Krüpple-like transcription factor subfamily of zinc finger proteins and has a tumor suppressor role in several types of cancer including cancer of the prostate, esophagus, colorectum, lung, pancreas and breast. KLF4 is frequently downregulated in prostate cancer cell lines compared to non-cancerous prostate cells and in prostate cancer tissues, especially in metastatic prostate cancer. Patients with a decreased KLF4 expression in tumor tissues compared to their normal counterparts have a significant higher risk for developing metastatic prostate cancer. Forced overexpression of KLF4 can inhibit prostate cancer cell growth/survival and cell cycle progression via modulating a number of cell cycle regulators including cyclin B1 and members of the Cip/Kip family. KLF4 overexpression can also suppress invasion and migration of prostate cancer cells through upregulating TIMP2. Our study suggests that KLF4 is strong predictor of PCa metastasis and may play an important role in governing key cell growth, motility and invasion events.