Autocrine signaling

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.

Interleukin-1

An example of an autocrine agent is the cytokine interleukin-1 in monocytes (see Interleukin). When interleukin-1 is produced in response to external stimuli, it can bind to cell-surface receptors on the same cell that produced it (see Interleukin receptors).

Wnt signaling pathway

Normally, the Wnt signaling pathway leads to stabilization of β-catenin (see Catenin) through inactivation of a protein complex containing the tumor suppressors Adenomatous polyposis coli (APC) and Axin. 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.

Interleukin 6

• Interleukins

Several studies have outlined the importance of autocrine IL-6 signaling in lung and breast cancers. For example, one group found a positive correlation between persistently activated tyrosine-phosphorylated STAT3 (pSTAT3), found in 50% of lung adenocarcinomas, and IL-6. Further investigation revealed that mutant EGFR could activate the oncogenic STAT3 pathway via upregulated IL-6 autocrine signaling. Similarly, HER2 overexpression occurs in approximately a quarter of breast cancers and correlates with poor prognosis. Recent research revealed that IL-6 secretion induced by HER2 overexpression activated STAT3 and altered gene expression, resulting in an autocrine loop of IL-6/STAT3 expression. Both mouse and human in vivo models of HER2-overexpressing breast cancers relied critically on this HER2–IL-6–STAT3 signaling pathway.