<i>FAT1 </i>gene in cancer and inflammation

摘要

The present invention demonstrates for the first time that FAT1 plays an important role in modulating PDCD4 expression, which in turn regulates AP-1 dependent transcription, controls processes crucial for migration and invasion in cancer cells, controls induction of a pro-inflammatory micro environment in cancer cells. The study illustrates a link between inflammation and cancer in cells or in a subject. This work highlights the importance of FAT1 in the induction of the cellular pathways of migration and invasion, proteolysis of the ECM and the expression of pro-inflammatory molecules leading to a favorable micro environment for tumor and cancer progression. The present invention also provides the use of FAT1 in regulating neoplastic phenotypes and genotypes including invasiveness and inflammatory micro environment of the cancer cells by acting as a novel apical regulator of a signaling pathway by affecting the AP1 transcriptional activity, affecting the property of both cell migration and invasion and at the same time affecting the expression of inflammatory modulators. The present invention also identifies a novel regulatory pathway for inflammatory mediators and inflammatory cellular responses via PDCD4 and AP1. The invention describes a pathway for the upregulation of inflammatory processes as such, and hence a means of regulating inflammatory pathologies in general.

主权项

1. A method of reducing the invasiveness into extracellular matrix of a tumor cell or of reducing migration of a tumor cell, said tumor cell overexpressing FAT1, comprising contacting said cell with or administering to said subject a pharmaceutical composition comprising a siRNA inhibitor of FAT1 expression or FAT1 activity, said siRNA inhibitor comprising the nucleotide sequence of SEQ ID NO: 2 and SEQ ID NO: 3.