Lipocalin 2 inhibits actin glutathionylation to promote invasion and migration

Author:

Choudhary Bhagya Shree12,Chaudhary Nazia12,Shah Manya1,Dwivedi Nehanjali3,P. K. Smitha4,Das Manjula3,Dalal Sorab Nariman12ORCID

Affiliation:

1. Cell and Tumor Biology, Advanced Centre for Treatment Research and Education in Cancer (ACTREC) Tata Memorial Centre Navi Mumbai India

2. Homi Bhabha National Institute Mumbai India

3. Molecular Immunology Mazumdar Shaw Medical Foundation Bommasandra, Bangalore India

4. Product Research Group Mazumdar Shaw Medical Foundation Bommasandra, Bangalore India

Abstract

Invasive and metastatic tumor cells show an increase in migration and invasion, making the processes contributing to these phenotypes potential therapeutic targets. Lipocalin 2 (LCN2; also known as neutrophil gelatinase‐associated lipocalin) is a putative therapeutic target in multiple tumor types and promotes invasion and migration, although the mechanisms underlying these phenotypes are unclear. The data in this report demonstrate that LCN2 promotes actin polymerization, invasion, and migration by inhibiting actin glutathionylation. LCN2 inhibits actin glutathionylation by decreasing the levels of reactive oxygen species (ROS) and by reducing intracellular iron levels. Inhibiting LCN2 function leads to increased actin glutathionylation, decreased migration, and decreased invasion. These results suggest that LCN2 is a potential therapeutic target in invasive tumors.

Funder

Advanced Centre for Treatment, Research and Education in Cancer

Department of Biotechnology, Ministry of Science and Technology, India

Publisher

Wiley

Subject

Cell Biology,Genetics,Molecular Biology,Biochemistry,Structural Biology,Biophysics

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