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Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Role of Liprins in the Regulation of Tumor Cell Motility and Invasion

Author(s): Sara Chiaretti and Ivan de Curtis

Volume 16, Issue 3, 2016

Page: [238 - 248] Pages: 11

DOI: 10.2174/156800961603160206124103

Price: $65

Abstract

Invasion leading to the formation of metastasis is one of the hallmarks of cancer. Analysis of different human cancers has led to the identification of the PPFIA1 gene encoding the protein liprin-α1, a possible player in cancer. The PPFIA1 gene is amplified in malignant tumors, including about 20% of breast cancers. Also the liprin-α1 protein is found overexpressed in tumors. Liprin-α1 belongs to the liprin family of cytosolic scaffold proteins that includes four liprin-α, two liprin-β members, and liprin-γ/kazrinE. In this review we will discuss the available evidence on the role of different members of the liprin family in distinct aspects of tumor cell migration and invasion. Evidence from in vitro studies indicates that the widely expressed liprin-α1 protein regulates the migration and invasion of human breast cancer cells. Liprin-α1 affects cell migration and invasion by regulating the organization of lamellipodia and invadopodia, two structures relevant to cell invasion. In the cell liprin-α1 forms a complex with liprin-β1, ERC1/ELKS and LL5 proteins, which localizes at the front of migrating cells and positively regulates lamellipodia stability, and integrin–mediated focal adhesions. On the other hand, liprin-β2 appears to play a role as tumor suppressor by inhibiting breast cancer cell motility and invasion. The available data indicate that liprins are central players in the regulation of tumor cell invasion, therefore representing interesting targets for anti-metastatic therapy.

Keywords: Breast cancer, cell motility, focal adhesions, invasion, liprins.

Graphical Abstract


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