We also propose a novel mechanism by which the tumor microenvironment could contribute to T cell dysfunction and shorter survival, i.e., diminished expression levels of essential signaling proteins, including STAT5B, PLCγ1 and NFATc2.
Taken together, our data suggest that (i) UCP2 is an important regulator of mitochondrial redox status and lipid signaling; (ii) hydrogen peroxide might mediate UCP2's tumor promoting activity; and (iii) pharmacological disruption of PLCγ-1 and/or hydrogen peroxide may have clinical utility for UCP2 overexpressed cancers.
Taken together, our study provides a mechanistic basis for the role for the PLCγ1-PKCγ pathway in regulating Hsp90α plasma membrane translocation, which facilitates tumor cell motility and promotes tumor metastasis.
In particular, phospholipase C-γ1 phosphorylation in sunitinib-resistant tumors was up-regulated by 2.6-fold compared with that in sunitinib-sensitive tumors (p<0.05).
In addition, analysis of 60 breast cancer patients' tissues revealed an increase of PLCgamma1 expression in metastasis compared with the primary tumor in 50% of tissues analyzed.