Autocrine

Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with paracrine signaling, intracrine signaling, or classical endocrine signaling. An example of an autocrine agent is the cytokine interleukin-1 in monocytes. When interleukin-1 is produced in response to external stimuli, it can bind to cell-surface receptors on the same cell that produced it. Another example occurs in activated T cell lymphocytes, i.e., when a T cell is induced to mature by binding to a peptide:MHC complex on a professional antigen-presenting cell and by the B7:CD28 costimulatory signal. Upon activation, "low-affinity" IL-2 receptors are replaced by "high-affinity" IL-2 receptors consisting of α, β, and γ chains. The cell then releases IL-2, which binds to its own new IL-2 receptors, causing self-stimulation and ultimately a monoclonal population of T cells. These T cells can then go on to perform effector functions such as macrophage activation, B cell activation, and cell-mediated cytoxicity. Tumor development is a complex process that requires cell division, growth, and survival. One approach used by tumors to upregulate growth and survival is through autocrine production of growth and survival factors. Autocrine signaling plays critical roles in cancer activation and also in providing self-sustaining growth signals to tumors. Normally, the Wnt signaling pathway leads to stabilization of β-catenin through inactivation of a protein complex containing the tumor suppressors APC and Axin. This destruction complex normally triggers β-catenin phosphorylation, inducing its degradation. De-regulation of the autocrine Wnt signaling pathway via mutations in APC and Axin have been linked to activation of various types of human cancer. Genetic alterations that lead to de-regulation of the autocrine Wnt pathway result in transactivation of epidermal growth factor receptor (EGFR) and other pathways, in turn contributing to proliferation of tumor cells.