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. 2021 Jun 23;4:778. doi: 10.1038/s42003-021-02303-x

Fig. 10. Schematic model of CSC-associated AKT/TSPYL5/PTEN loop signaling pathway.

Fig. 10

TSPYL5-mediated signaling pathway, which regulates the expression of ALDH1, CD44, and PTEN, enforces cancer stemness in a positive feedback manner. It is initiated by AKT-dependent phosphorylation of TSPYL5, followed by suppression of PTEN expression and consequent activation of AKT. TSPYL5 is a critical component of the CSC-associated loop signaling pathway. On the other hand, TSPYL5-depleted cells by promoter methylation or protein degradation are hard to maintain cancer stemness, resulting in high sensitivity to radio- or chemotherapy. Therefore, the strategies for TSPYL5 depletion, which can disrupt the self-renewal program of CSCs, can be novel methods for cancer treatment.