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PTPRN 2 and PLC β1 promote metastatic breast cancer cell migration through PI (4,5)P 2 ‐dependent actin remodeling
Author(s) -
Sengelaub Caitlin A,
Navrazhina Kristina,
Ross Jason B,
Halberg Nils,
Tavazoie Sohail F
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201591973
Subject(s) - library science , cancer , biology , systems biology , computational biology , computer science , genetics
Altered abundance of phosphatidyl inositides ( PI s) is a feature of cancer. Various PI s mark the identity of diverse membranes in normal and malignant cells. Phosphatidylinositol 4,5‐bisphosphate ( PI (4,5)P 2 ) resides predominantly in the plasma membrane, where it regulates cellular processes by recruiting, activating, or inhibiting proteins at the plasma membrane. We find that PTPRN 2 and PLC β1 enzymatically reduce plasma membrane PI (4,5)P 2 levels in metastatic breast cancer cells through two independent mechanisms. These genes are upregulated in highly metastatic breast cancer cells, and their increased expression associates with human metastatic relapse. Reduction in plasma membrane PI (4,5)P 2 abundance by these enzymes releases the PI (4,5)P 2 ‐binding protein cofilin from its inactive membrane‐associated state into the cytoplasm where it mediates actin turnover dynamics, thereby enhancing cellular migration and metastatic capacity. Our findings reveal an enzymatic network that regulates metastatic cell migration through lipid‐dependent sequestration of an actin‐remodeling factor.