Abstract
Proteins of the evolutionary conserved family of partitioning-defective (Par) genes have emerged as key regulators of polarity and thus of cell and tissue architecture. Par proteins mediate a variety of cellular processes and couple control of cell shape to crucial signaling pathways regulating growth and survival, metabolism, cell fate, and differentiation. Alterations in adhesion, polarity, and architecture of tumor cells are hallmarks of cancer and implicated in tumor growth, invasion, and metastasis. Seminal work in Drosophila and mammalian cell culture suggested a molecular connection between the regulation of polarity and oncogenic processes. Recent advance stems from different mouse models revealing a causal link between polarity protein dysfunction and the formation and progression of cancer starting to shed light into some underlying mechanisms. It has become apparent that polarity signaling impacts on a multitude of processes involved in tumor formation and progression and that significant context dependency exists.
This chapter provides an overview of physiological processes that when disturbed facilitate tumor formation. Recent evidence from model organisms implicating Par protein dysfunction in the onset and progression of cancer is summarized. As Par proteins are tightly connected to aPKC signalling, data regarding a role of aPKC in cancer is also presented. Important findings from invertebrate tumor models will be reviewed, though the chapter focuses on functional data derived from mammalian systems.
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We are grateful for the financial and/or infrastructural support by the Excellence Initiative by the German federal and state governments (CECAD Cologne), the German Research Foundation (CRC829 and CRC832), Köln Fortune, the Stiftung Kölner Krebsforschung (EI—Exzellenz Initiieren), and the Center for Molecular Medicine Cologne (CMMC).
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Mescher, M., Iden, S. (2015). Par Proteins in Tumor Formation and Progression. In: Ebnet, K. (eds) Cell Polarity 2. Springer, Cham. https://doi.org/10.1007/978-3-319-14466-5_6
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