Tumor-associated carbohydrate antigens (TACA) result from the aberrant glycosylation that is seen with transformation to a tumor cell. The carbohydrate antigens that have been found to be tumor-associated include the mucin related Tn, Sialyl Tn, and Thomsen-Friedenreich antigens, the blood group Lewis related LewisY, Sialyl LewisX and Sialyl LewisA, and LewisX, (also known as stage-specific embryonic antigen-1, SSEA-1), the glycosphingolipids Globo H and stage-specific embryonic antigen-3 (SSEA-3), the sialic acid containing glycosphingolipids, the gangliosides GD2, GD3, GM2, fucosyl GM1, and Neu5GcGM3, and polysialic acid. Recent developments have furthered our understanding of the T-independent type II response that is seen in response to carbohydrate antigens. The selection of a vaccine target antigen is based on not only the presence of the antigen in a variety of tumor tissues but also on the role this antigen plays in tumor growth and metastasis. These roles for TACAs are being elucidated. Newly acquired knowledge in understanding the T-independent immune response and in understanding the key roles that carbohydrates play in metastasis are being applied in attempts to develop an effective vaccine response to TACAs. The role of each of the above mentioned carbohydrate antigens in cancer growth and metastasis and vaccine attempts using these antigens will be described.

Background:After activation by phosphorylation, phospho-AKT (pAKT) is translocated to nucleus. Results: Ubiquitination of pAKT by NEDD4-1 is coupled to AKT activation at the plasma membrane by insulin-like growth factor (IGF)-1, which promotes pAKT nuclear trafficking. Conclusion: NEDD4-1 is an E3 ligase for pAKT specifically involved in pAKT nuclear trafficking in IGF-1 signaling. Significance: AKT activation and proper subcellular localization requires specific E3 ligases in a ligand-specific manner.

SUMMARY Protein kinase C (PKC) isozymes are commonly recognized as oncoproteins based on their activation by tumor-promoting phorbol esters. However, accumulating evidence indicates that PKCs can be inhibitory in some cancers, with recent findings propelling a shift in focus to understanding tumor suppressive functions of these enzymes. Here, we report that PKCα acts as a tumor suppressor in PI3K/AKT-driven endometrial cancer. Transcriptional suppression of PKCα is observed in human endometrial tumors in association with aggressive disease and poor prognosis. In murine models, loss of PKCα is rate limiting for endometrial tumor initiation. PKCα tumor suppression involves PP2A-family-dependent inactivation of AKT, which can occur even in the context of genetic hyperactivation of PI3K/AKT signaling by coincident mutations in PTEN, PIK3CA, and/or PIK3R1. Together, our data point to PKCα as a crucial tumor suppressor in the endometrium, with deregulation of a PKCα→PP2A/PP2A-like phosphatase signaling axis contributing to robust AKT activation and enhanced endometrial tumorigenesis.

Background: Mechanisms of activation-induced PKC down-regulation are poorly understood. A characterized pathway involves priming site dephosphorylation and degradation of the dephosphorylated species. Results: Mature, fully phosphorylated PKC␣ is a major target for activation-induced degradation, via mechanisms controlled by Hsps. Conclusion: Hsps control phosphorylation and degradation of fully primed, activated PKC. Significance: Findings from this study support a new model of PKC desensitization.