Work

Integrin-binding Protein Nischarin Interacts with Tumor Suppressor Liver Kinase B1 (LKB1) to Regulate Cell Migration of Breast Epithelial Cells

Year: 2013

Type: article

Abstract: Biallelic inactivation of LKB1, a serine/threonine kinase, has been detected in 30% of lung adenocarcinomas, and inhibition of breast tumor growth has been demonstrated. We have identified the tumor suppressor, Nischarin, as a novel binding partner of LKB1. Our mapping analysis shows that the N terminus of Nischarin interacts with amino acids 44–436 of LKB1. Time lapse microscopy and Transwell migration data show that the absence of both Nischarin and LKB1 from an invasive breast cancer cell line (MDA-MB-231) enhances migration as measured by increased distance and speed of migrating cells. Our data suggest that this is a result of elevated PAK1 and LIMK1 phosphorylation. Moreover, the absence of Nischarin and LKB1 increased tumor growth in vivo . Consistent with this, the percentage of S phase cells was increased, as demonstrated by flow cytometry and enhanced cyclin D1. The absence of Nischarin and LKB1 also led to a dramatic increase in the formation of lung metastases. Our studies, for the first time, demonstrate functional interaction between LKB1 and Nischarin to inhibit cell migration and breast tumor progression. Mechanistically, we show that these two proteins together regulate PAK-LIMK-Cofilin and cyclin D1/CDK4 pathways. Background: This work examines the importance of interaction between Nischarin and LKB1. Results: Nischarin and LKB1 interact in vivo . Absence of Nischarin and LKB1 increases cell migration and tumor growth. Conclusion: This is the first report showing that two suppressors work in concert to inhibit cell migration. Significance: Understanding the mechanisms of regulation of tumor suppressors may have many therapeutic advantages.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m112.418103

Authors: Prachi Jain, Somesh Baranwal, Shengli Dong, Amanda P. Struckhoff, Rebecca A. Worthylake, Suresh K. Alahari

Institutions: Louisiana State University, Louisiana State University Health Sciences Center New Orleans

Language: English

Topic: Mechanisms of cancer metastasis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430