Proline-Directed Protein Kinase FA as a Potential Target for Diagnosis and Therapy of Human Cancers

Shiaw-Der      Yang

Abstract

Proline-directed protein kinase FA (PDPK FA) was originally identified as a phosphatase activating factor (FA) but has subsequently been characterized as a multisubstrate / multifunctional PDPK possibly associated with human cancers. In recent years, the immunohistochemical study revealed that PDPK FA was highly expressed in tumor mass and preferentially overexpressed in the invasive lesions of the resected tissue sections obtained from various types of cancer patients. The clinicopathologic study further revealed a close correlation of the overexpression of PDPK FA with poor prognosis of the cancer patients. The antisense gene therapy study also confirmed that due to its multisubstrate / multifunctional PDPK nature, the overexpression of PDPK FA is essential for the development of malignant growth, tumorigenesis, invasion, metastasis, antidifferentiation, anti-apoptosis and chemoresistance in human cancers. From immunohistochemical, clinicopathologic and antisense gene therapeutic studies combined together, PDPK FA has emerged as a key regulator of all aspects of neoplasia. In this way, nature provides prima facie evidence of a particular protein kinases pivotal importance to the neoplastic state. PDPK FA therefore represents a newly-described, previously-undiscovered novel signal transducing target for diagnosis, disease monitoring, drug screening and therapy of human cancers.

Keywords: tumorigenesis, invasion, metastasis, apoptosis, differentiation, chemoresistance

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