Receptor Protein Tyrosine Phosphatases, cell-cell adhesion and signal transduction: We are studying the role of receptor protein tyrosine phosphatases (RPTPs) in signals transduced upon cell-cell contact. Some RPTPs such as PTPµ have cell adhesion molecule-like extracellular segments and are involved in adhesion-dependent signaling. PTPµ mediates adhesion by binding homophilically, i.e., PTPµ on the surface of one cell binds to PTPµ on an apposing cell. Interestingly, we found that PTPµ associates with another family of cell adhesion molecules called cadherins. Cadherins are adhesion molecules that play a role in cytoskeletal organization and cell junction formation. We are investigating the role of RPTPs and tyrosine phosphorylation in assembly and signal transduction at sites of cell-cell adhesion.
RPTPs and cancer: We are investigating the role of RPTPs in cell growth and malignancy in cancer. Protein tyrosine kinases can cause uncontrolled cell growth by disrupting the balance of cellular phosphotyrosine levels suggesting that PTPs may play an important role in negative growth regulation or could function as tumor suppressors. In this regard, we have recently found that certain cancer cells have lost PTPµ expression. Therefore, we are determining whether restoration of PTPµ expression in cancer cells results in changes in adhesion, growth, tumorigenicity or metastasis.
Kaur H, Burden-Gulley SM, Phillips-Mason PJ, Basilion JP, Sloan AE, Brady-Kalnay SM. Protein tyrosine phosphatase mu regulates glioblastoma cell growth and survival in vivo. Neuro Oncol. 2012 Apr 14. [Epub ahead of print] [PubMed]
Kaur H, Phillips-Mason PJ, Burden-Gulley SM, Kerstetter-Fogle AE, Basilion JP, Sloan AE, Brady-Kalnay SM. Cadherin-11, a marker of the mesenchymal phenotype, regulates glioblastoma cell migration and survival in vivo. Mol Cancer Res. 2012 Mar;10(3):293-304. Epub 2012 Jan 20. [PubMed]
Burden-Gulley SM, Qutaish MQ, Sullivant KE, Lu H, Wang J, Craig SE, Basilion JP, Wilson DL, Brady-Kalnay SM. Novel cryo-imaging of the glioma tumor microenvironment reveals migration and dispersal pathways in vivid three-dimensional detail. Cancer Res. 2011 Sep 1;71(17):5932-40. Epub 2011 Aug 23. [PubMed]
Phillips-Mason PJ, Craig SE, Brady-Kalnay SM. Should I stay or should I go? Shedding of RPTPs in cancer cells switches signals from stabilizing cell-cell adhesion to driving cell migration. Cell Adh Migr. 2011 Jul 1;5(4):298-305. Epub 2011 Jul 1. [PubMed]
Craig SE, Brady-Kalnay SM. Tumor-derived extracellular fragments of receptor protein tyrosine phosphatases (RPTPs) as cancer molecular diagnostic tools. Anticancer Agents Med Chem. 2011 Jan;11(1):133-40. Review. [PubMed]
Craig SE, Brady-Kalnay SM. Cancer Cells Cut Homophilic Cell Adhesion Molecules and Run. Cancer Res. 2010 Nov 17. [PubMed]
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