Fig. 1.

JNK signaling enhances the compensatory proliferation of the neighboring cells, stem cells or cancer stem cells (CSCs). In response to stress signals, activated JNK induces the release of Wnt/BMP and IL-6 from the stressed cells in which an apoptotic response might be initiated but not yet completed, thus inducing a state of “undead” cells. The released Wnt/BMP and IL-6 interact with Fz and JAK complexes, respectively, on the surface of the neighboring cells, stem cells or CSCs, which is followed by the activations of the β-catenin/TCF and Stat3 signaling pathways in these cells. Both β-catenin/TCF and Stat3 are capable of enhancing the expression of the genes such as CCND1, OCT4, Sox2, KLF4, c-Myc, CD44, and others that are important for the cell proliferation and self-renewal of the stem cells or CSCs. There is a reciprocal positive feedback between Stat3 and JNK signaling in the non-stressed neighboring cells or stem cells. Alternatively, JNK can affect Stat3 through the suppression of Hpo/Wts (MST/LATS in mammals) to alleviate Yki (YAP in mammals) that can induce Stat3 through IL-6 signaling. Similarly, in addition to the regulation of the β-catenin/TCF pathway, the Wnt signaling can regulate the cell growth of stem cells by suppressing Notch, a repressor of c-Myc and other cell cycle genes. Circled arrow indicates a group of genes important for the self-renewal of the stem cells or CSCs.