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.
VEGF
Another agent involved in autocrine cancer signaling is vascular endothelial growth factor (VEGF). VEGF, produced by carcinoma cells, acts through paracrine signaling on endothelial cells and through autocrine signaling on carcinoma cells.
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.
Interleukins:
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).
Interleukin 6
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.
Interleukin 7
A study demonstrates how the autocrine production of the IL-7 cytokine mediated by T-cell acute lymphoblastic leukemia (T-ALL) can be involved in the oncogenic development of T-ALL and offer novel insights into T-ALL spreading.
