Activation of T-cell Protein Tyrosine Phosphatase Suppresses Keratinocyte Survival and Proliferation Following UVB Irradiation [Cell Biology]

November 18th, 2014 by Lee, H., Morales, L. D., Slaga, T. J., Kim, D. J.

Chronic exposure of UV radiation can contribute to the development of skin cancer by promoting PTK signaling. Studies show that exposure to UV radiation increases the ligand-independent activation of PTKs and induces PTP inactivation. In the present work, we report that TC-PTP activity is stimulated during the initial response to UVB irradiation which leads to suppression of keratinocyte cell survival and proliferation via the down-regulation of STAT3 signaling. Our results show that TC-PTP-deficient keratinocyte cell lines expressed a significantly increased level of phosphorylated STAT3 after exposure to low dose UVB. This increase corresponded with increased cell proliferation in TC-PTP-deficient keratinocytes following UVB irradiation. Loss of TC-PTP also reduced UVB-induced apoptosis. In corroboration with these results, overexpression of TC-PTP in keratinocyte cell lines yielded a decrease in phosphorylated STAT3 levels, which corresponded with a significant decrease in cell proliferation in response to low dose UVB. We demonstrate that TC-PTP activity was increased upon UVB exposure and overexpression of TC-PTP in keratinocyte cell lines further increased its activity in the presence of UVB. Treatment of TC-PTP-deficient keratinocytes with the STAT3 inhibitor STA21 significantly reduced cell viability following UVB exposure in comparison with untreated TC-PTP-deficient keratinocytes, confirming that the effect of TC-PTP on cell viability is mediated by STAT3 dephosphorylation. Combined, our results indicate that UVB-mediated activation of TC-PTP plays an important role in the STAT3-dependent regulation of keratinocyte cell proliferation and survival. Furthermore, these results suggest that TC-PTP may be a novel potential target for the prevention of UVB-induced skin cancer.
  • Posted in Journal of Biological Chemistry, Publications
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