GLi proteins belong to the family of zinc finger transcription factors and act at the distal end of the Hedgehog (HH) signaling pathway to control HH target gene transcription.
An overview of Gli
Hedgehog (Hh) signaling pathway is an important signaling pathway to regulate cell proliferation and tissue differentiation during human embryonic development. Recent studies have found that abnormal activation can lead to a variety of cancers, such as lung cancer, gastrointestinal cancer, and prostate cancer. Gli is a transcription regulatory factor at the end of the Hh signaling pathway and has a strong transcriptional activation function. At the same time, Gli can transfer the Hh signaling of out-of-cells to the nucleus to initiate transcription of the target gene
Major types of Gli
There are three major nuclear transcription factors, including Gli-1, Gli-2, and Gli-3, which play an important role in vertebrates. Among them, Gli-1 is a direct transcription activator. Its activation regulation occurs at the transcription level and is a reliable indicator of the activity of Hh signaling pathways while Gli-2 and Gli-3 are potential transcription activators.
Inhibition of Gli
GANT-61 is an inhibitor of Gli1 and Gli2, used for cancer research. GANT-61 inhibits cell viability and induces apoptosis in pancreatic cancer stem cells (CSCs). GANT-61 can differentially regulate genes involved in cell survival, cell death and pluripotency. GANT-61 inhibits motility, invasion and migration of CSCs.
Gli and diseases
It is believed that Gli may induce tumor directly through the following mechanisms: (1) Induce the expression of cell cycle regulated protein in G1/S to promote cell proliferation; (2) Directly induce anti-apoptotic factor bcl-2 expression to inhibit apoptosis; (3) Direct activation can promote the transcription of epithelial cells to interstitial transformation factors to improve the invasiveness of tumors. The studies have shown that Gli-1 ~ 3 show high expression in squamous cell carcinoma and cervical intradermal neoplasia 2 (CIN2), CIN3, and do not express or appear weak positive in normal cervical cancer tissue. Gli-2 is expressed in almost all squamous cell carcinoma and CIN 1~ 3 in the nucleus of the tissue. And the positive percentage of Gli-1 is lower than that of Gli-2 in squamous cell carcinoma and CIN-2 and CIN-3 tissue. Therefore, it can be speculated that in the process of cervical cancer, Gli-2 is more important than Gli-1.