INGs or Inhibitor of Growth proteins act as type II tumor suppressors in epithelial cancers. The senescence associated secretory phenotype (SASP) is a phenomenon where senescent cells secrete a defined group of proteins including various proinflammatory cytokines. Cancer-associated fibroblasts (CAFs) are another component of the tumor microenvironment secreting various growth factors, proinflammatory cytokines and proteases. The proinflammatory cytokines secreted by CAFs and senescent cells as SASP cause chronic inflammation, which is one of the hallmarks of cancer.
Although generally described as a tumor suppressor, our lab has recently reported that higher ING1 levels in the stroma correlate with poor survival outcome in breast cancer patients. To better understand this, we examined the effects of altering ING1b levels in fibroblasts. We find that ING1b increases the secretion of IL8, IL6, CXCL1 and CCL7 (also secreted by CAFs and in the SASP). This most likely occurs by ING1b activating NF-κB. Factors secreted by fibroblasts in response to ING1b also enhances the growth and migration capacity of several lines of breast cancer cells and also induce a cancer like phenotype of migration and growth in normal breast epithelial cells.