Inositol-1,4,5-trisphosphate-3-kinase-A is a new cell motility-promoting protein that increases the metastatic potential of tumour cells by two functional activities.


Cellular migration is an essential prerequisite for metastatic dissemination of cancer cells. The present study demonstrates that the neuron/testis specific F-actin targeted inositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) is ectopically expressed in different human tumour cell lines, and during tumour progression in the metastatic tumour model Balb-neuT. High expression of ITPKA increases invasive migration in vitro and metastasis in a xenograft SCID mouse model. Mechanistic studies show that ITPKA promotes migration of tumour cells by two different mechanisms: Growth factor independently, high levels of ITPKA induce the formation of large cellular protrusions by directly modulating the actin cytoskeleton. The F-actin binding activity of ITPKA stabilizes and bundles actin filaments and thus increases the levels of cellular F-actin. In growth factor stimulated cells, the catalytically active domain enhances basal ITPKA induced migration by activating store-operated calcium entry through production of inositol-1,3,4,5-tetrakisphosphate and subsequent inhibition of inositol-phosphate-5-phosphatase. These two functional activities of ITPKA stimulating tumour cell migration place the enzyme among the potential targets of anti-metastatic therapy.

Bibliographical data

Original languageGerman
Article number8
Publication statusPublished - 2010
pubmed 20022963