GFRA1: A Novel Molecular Target for the Prevention of Osteosarcoma Chemoresistance

The glycosylphosphatidylinositol-linked GDNF (glial cell derived neurotrophic factor) receptor alpha (GFRA), a coreceptor that recognizes the GDNF family of ligands, has a crucial role in the development and maintenance of the nervous system. Of the four identified GFRA isoforms, GFRA1 specifically recognizes GDNF and is involved in the regulation of proliferation, differentiation, and migration of neuronal cells. GFRA1 has also been implicated in cancer cell progression and metastasis. Recent findings show that GFRA1 can contribute to the development of chemoresistance in osteosarcoma. GFRA1 expression was induced following treatment of osteosarcoma cells with the popular anticancer drug, cisplatin and induction of GFRA1 expression significantly suppressed apoptosis mediated by cisplatin in osteosarcoma cells. GFRA1 expression promotes autophagy by activating the SRC-AMPK signaling axis following cisplatin treatment, resulting in enhanced osteosarcoma cell survival. GFRA1-induced autophagy promoted tumor growth in mouse xenograft models, suggesting a novel function of GFRA1 in osteosarcoma chemoresistance

Role of TC-PTP-mediated regulation of STAT1 in skin carcinogenesis

STAT1 has been shown to have tumor suppressive or protumorigenic roles in tissues in a context-dependent manner. In this study, we explored the role of TC-PTP in the regulation of STAT1 during skin tumor promotion. We found that the levels of the phosphorylated serine form of STAT1 were increased in TC-PTP overexpressing keratinocytes in response to TPA treatment. Additionally, TC-PTP overexpression decreased TPA-induced proliferation through regulation of STAT1 signaling. These results suggest that positive regulation of STAT1 signaling via TC-PTP can have a protective role towards keratinocytes during tumor promotion. These findings suggest that targeting TC-PTP-mediated regulation of STAT1 signaling could have therapeutic implications for treating or preventing skin cancer

Protein Tyrosine signaling and its potential therapeutic implications in carcinogenesis

Protein tyrosine phosphorylation is a crucial signaling mechanism that plays a role in epithelial carcinogenesis. Protein tyrosine kinases (PTKs) control various cellular processes including growth, differentiation, metabolism, and motility by activating major signaling pathways including STAT3, AKT, and MAPK. Genetic mutation of PTKs and/or prolonged activation of PTKs and their downstream pathways can lead to the development of epithelial cancer. Therefore, PTKs became an attractive target for cancer prevention. PTK inhibitors are continuously being developed, and they are currently used for the treatment of cancers that show a high expression of PTKs. Protein tyrosine phosphatases (PTPs), the homeostatic counterpart of PTKs, negatively regulate the rate and duration of phosphotyrosine signaling. PTPs initially were considered to be only housekeeping enzymes with low specificity. However, recent studies have demonstrated that PTPs can function as either tumor suppressors or tumor promoters, depending on their target substrates. Together, both PTK and PTP signal transduction pathways are potential therapeutic targets for cancer prevention and treatment

Phase Stability and Physical Properties of Cubic and Tetragonal ZrO 2 in the System ZrO 2 –Y 2 O 3 –Ta 2 O 5

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65531/1/j.1151-2916.1991.tb04302.x.pd

Particulate counter electrode system for enhanced light harvesting in dye-sensitized solar cells

A particulate counter electrode with photo scattering and redox catalytic properties is applied to dye sensitized solar cells (DSSCs) in order to improve photo conversion efficiency and simplify the assembly process. Our particulate counter electrode acts as both a photo reflecting layer and a catalyst for reduction of electrolyte. The reflective and catalytic properties of the electrode are investigated through optical and electrochemical analysis, respectively. A short circuit current density enhancement is observed in the DSSCs without the need to add an additional reflecting layer to the electrode. This leads to a simplified assembly process. (C) 2013 Optical Society of Americ

TC-PTP overexpression attenuates skin cancer formation during environmental skin carcinogenesis

Background: T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, has been shown to function as a tumor suppressor during skin carcinogenesis. Methods: we generated a novel epidermal specific TC-PTP-overexpressing (K5HA.Ptpn2) mouse model to show that TC-PTP contributes to the attenuation of chemically induced skin carcinogenesis through the synergistic regulation of STAT1, STAT3, STAT5, and PI3K/AKT signaling. Results: We found overexpression of TC-PTP increased epidermal sensitivity to DMBA-induced apoptosis and it decreased TPA-mediated hyperproliferation, coinciding with reduced epidermal thickness. Inhibition of STAT1, STAT3, STAT5 or AKT reversed the effects of TC-PTP overexpression on epidermal survival and proliferation. Mice overexpressing TC-PTP in the epidermis developed significantly reduced numbers of tumors during skin carcinogenesis and presented a prolonged latency of tumor initiation. Examination of human papilloma and squamous cell carcinomas (SCCs) revealed that TC-PTP expression was significantly reduced and TC-PTP expression was inversely correlated with the increased grade of SCCs. Conclusion: Our findings demonstrate that TC-PTP is a potential therapeutic target for the prevention of human skin cancer given that it is a major negative regulator of oncogenic signaling