In non-cancerous cells, phosphorylated proteins exist transiently, becoming de-phosphorylated by specific phosphatases that terminate propagation of signaling pathways. In cancers, compromised phosphatase activity and/or expression occur and contribute to tumor phenotype. The non-receptor phosphatase, PTPN13, has recently been dubbed a putative tumor suppressor. It decreased expression in breast cancer correlates with decreased overall survival. Here we show that PTPN13 regulates a new signaling complex in breast cancer consisting of ErbB2, Src, and EphrinB1. To our knowledge, this signaling complex has not been previously described. Co-immunoprecipitation and localization studies demonstrate that EphrinB1, a PTPN13 substrate, interacts with ErbB2. In addition, the oncogenic V660E ErbB2 mutation enhances this interaction, while Src kinase mediates EphrinB1 phosphorylation and subsequent MAP Kinase signaling. Decreased PTPN13 function further enhances signaling. The association of oncogene kinases (ErbB2, Src), a signaling transmembrane ligand (EphrinB1) and a phosphatase tumor suppressor (PTPN13) suggest that EphrinB1 may be a relevant therapeutic target in breast cancers harboring ErbB2-activating mutations and decreased PTPN13 expression.

Human papillomavirus (HPV)-related disease is a significant health problem in the United States and throughout the world, especially in developing countries. Standard treatment to date has been surgical excision, but we ask the question “For what other clinically evident, virally mediated disease is the standard of treatment surgery?” The authors performed a systematic literature review and selected articles most relevant to the topic. This article reviews prevention, chemoprevention, and vaccine trials for the prevention and treatment of HPV-related disease of the genital tract. Significant advances have been made in the last decade, and the future holds promise for effective nonsurgical options for the patients with cervical dysplasia and other HPV-associated diseases.

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Tyrosine kinases, like the ErbB and Src families, can mediate potent oncogenic growth and are successful therapeutic targets of human cancers. However, many cancer cells overcome or successfully modulate these downstream signaling cascades in the absence of growth factor or kinase over-expression. We have previously identified a cellular phosphatase, PTPN13 that significantly modulates mitogenic signaling and can function as tumor suppressors. Decreased PTPN13 expression enhances ErbB2-mediated MAP Kinase activation, and is also associated with decreased survival in breast cancer. Here we show that PTPN13 regulates a signaling complex consisting of ErbB2, Src, and EphrinB1. To our knowledge, this signaling complex has not been previously described. Co-immunoprecipitation, proximity ligation assay and immunofluoroscence studies demonstrate that EphrinB1, a PTPN13 substrate, interacts with ErbB2. In addition, the oncogenic V660E ErbB2 mutation enhances this interaction, while Src kinase mediates EphrinB1 phosphorylation and subsequent MAP Kinase signaling. Decreased PTPN13 function further potentiates these changes. The association of oncogene kinases (ErbB2, Src), a signaling transmembrane ligand (EphrinB1) and a phosphatase tumor suppressor (PTPN13) suggest that EphrinB1 may be a relevant therapeutic target in cancers harboring ErbB2-activating mutations and decreased PTPN13 expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-143. doi:1538-7445.AM2012-LB-143