Sign up for Table of Contents Alerts.

Email this page

Print this page

Perspectives

Non-Canonical Activation of GLI Transcription Factors: Implications for Targeted Anti-Cancer Therapy

Matthias Lauth and Rune Toftgård

Purchase article for $19

Subscribe to this journal for $129/year

GLI transcription factors constitute the final effectors of the Hedgehog (HH) signaling pathway. In many tumors, such as those of the pancreas, prostate, skin or lung, ectopic activation of GLI proteins has been linked to tumorigenesis. In several of these cases, HH ligand- or receptor-induced signaling (canonical HH signaling) was found to be the cause underlying GLI activation. Recent evidence points towards additional, non-canonical, mechanisms of GLI activation. Here we review findings on the crosstalk of two HH-unrelated signaling pathways (RAS and Transforming growth factor β) to the HH pathway downstream of the signaling component Smoothened. Both pathways stimulate and/or induce GLI1 and GLI2 activity independent of the presence of HH ligands. We also discuss the putative roles of these crosstalk mechanisms for tumor cell metastasis. The emerging picture of GLI transcription factors as an integrative platform of numerous signaling inputs has important implications for the understanding of tumor development and argues for inclusion of targets acting downstream of the receptor level in the design of current drug development programs.

Authors

Matthias Lauth

Karolinska Institutetl Huddinge, Sweden

Rune Toftgård

Karolinska Institutetl Huddinge, Sweden

Purchase article for $19

Subscribe to this journal for $129/year