**3.3 Inflammatory signaling molecules**

Proinflammatory cytokines are like TNF-α, IL-1, and IL-6, and their cell membrane receptors association influences downstream signaling factors activation. Moreover, colon cancer-associated inflammatory molecules are NF-κB and STAT-3, activated by binding the lipopolysaccharides to the toll-like receptor (TLR)-II and IV. NF-κB and STAT-3 actions enhance apoptosis of the cells and increase the expression of TNF-α, IL-1, and IL-6. However, STAT-3 and NF-κB are negatively correlated with the TGF-β release from cancer cells or with the TGF-β receptor expression on cancer cells, especially colon cancer [2, 24].

**Figure 5.**

*The chemokines and cytokines and colorectal cancer growth interrelations [32].*

*Colorectal Cancer Stages, Progress, Genetic Predisposition, and Immune Surveillance DOI: http://dx.doi.org/10.5772/intechopen.105982*

### *3.3.1 NF-κB and STAT-3*

The proinflammatory signaling molecules NF-κB and STAT-3 were associated with multiple types of hyper-inflammatory diseases or hyper-inflammatory foundations, such as inflammatory bowel syndrome, CC, lung cancer, and many other types of cancer. The higher levels of NF-κB and STAT-3 in the long term were correlated with CC angiogenesis and invasiveness. The activation of NF-κB mediator by TNF-α and IL-1β and the activation of STAT-3 mediator by IL-6 have led to cancer growth through the oncogenic signaling pathways activation in cancer cells (i.e. KRAS overexpression). On the other hand, their short-term secretions were reported to induce cancer cell apoptosis (proapoptotic) [13, 23].
