Figure 3.

Homo- and Heterocellular Oncogenic Signaling. (A) Similarly to many cancers, colorectal cancer (CRC) is often viewed as a homocellular system (i.e., only epithelial cancer cells are studied). When viewed from this homocellular perspective, epithelial oncogenic mutations can only drive malignant phenotypes through cell-autonomous signaling (e.g., loss of APC function hyperactivates epithelial β-catenin signaling). (B) However, because CRC tumors are explicitly heterocellular (Figure 1), oncogenic mutations can explore a wide range of heterocellular signaling options. This heterocellular diversity increases oncogenic signaling opportunities (e.g., cell-autonomous, non cell-autonomous, and reciprocal signaling) – enabling tumors to achieve complex emergent malignant phenotypes.