GLI3 (GLI Family Zinc Finger 3)

Increased levels of Gli3 repressor (Gli3-REP) and decreased GSK-3β phosphorylation further confirmed Hedgehog pathway inhibition. In conclusion, the current study provides the first evidence that CAN, CGA, and their combination modulate the Hedgehog pathway, suggesting their potential as novel therapeutic strategies for IPF.

By comparing treatment and culture context independently, cyclopamine-mediated SHH inhibition and astrocyte-dependent signals use distinct but interacting effects on cell behavior...Astrocyte co-culture significantly modulates the molecular and phenotypic response of GBM cells to SHH inhibition, reshaping apoptotic and proliferative behaviors in both CSCs and bulk populations. These findings highlight the critical importance of the tumor microenvironment in therapeutic response and suggest that effective targeting of SHH signaling may require models that account for astroglial interactions.

Finally, we showed that VAV1 is necessary for the binding of GLI1 and its coactivator the histone acetyltransferase PCAF to this regulatory element. Taken together, our data supports a role for VAV1 in GLI1 transcriptional regulation, elucidating a new mechanism of function for nuclear VAV1 in PDAC cells.

E0703 alleviated IR-induced DNA damage in lymphocytes by selectively targeting ERβ. The formation of the eIF4F complex in a GLI3-dependent manner was critical for ATM-CHK2 activation triggered by E0703. Our study provides an alternative countermeasure to alleviate IR-induced lymphopenia in individuals undergoing radiotherapy or IR-related diagnosis.

Interestingly, dorsomorphin inhibited the expression and nucleation of Gli1 and Gli3 but not affected the expression of Gli2. Thus, these findings reveal that the new mechanism of AMPK inhibitor dorsomorphin against prostate cancer metastasis is through synergistically antagonizing JAK2/STAT3 and Gli2-independent Shh activation.

Our results indicate that gingerol promoted the upregulation of miR-506, leading to the induction of apoptosis in ovarian cancer cells. This study supports the potential of 6-gingerol-based therapy for ovarian malignancies.

By comparing treatment and culture context independently, cyclopamine-mediated SHH inhibition and astrocyte-depending signals use distinct but interacting effects on cell behavior...Astrocyte co-culture significantly modulates the molecular and phenotypic response of GBM cells to SHH inhibition, reshaping apoptotic and proliferative behaviors in both CSCs and bulk populations. These findings highlight the critical importance of the tumor microenvironment in therapeutic response and suggest that effective targeting of SHH signaling may require models that account for astroglial interactions.

Notably, higher expression levels of SUFU were associated with a negative impact on ovarian cancer patients under many clinical-histopathological aspects. These results shed new light on the role of these genes in the chemoresponsiveness of ovarian cancer, especially SUFU, which could be considered a novel indicator for poor prognosis in epithelial ovarian cancer.

This, in turn, triggers the cell-autonomous production of steroids that prostate cancer relies on, in line with the enhanced responsiveness of SPOP-mutated prostate cancer to androgen deprivation therapy. These data demonstrate that germline variants dictate men's prostate cancer somatic evolution and suggest opportunities to jointly model germline-somatic tandems to help untangle the complexity of human cancer.

These findings shed light on novel genetic mutations and osteocyte transcriptome-related molecular pathways involved in CPT, providing a new framework for understanding the genetic regulation of CPT pathology and suggesting potential directions to further elucidate its pathogenesis.

several lines of evidence suggest that these genes are of potential clinical impact in lung cancer even though they have not been correlated with lung cancer in the OMIM database or other genetic databases. Therefore, these genes deserve further investigations: segregation analysis, enlarged cohorts and in vitro/in vivo studies could help to clarify their role in lung cancer.

Additional investigations reveal that dihydroartemisinin (DHA) effectively impedes ESCC cell metastasis by suppressing SRPK1-mediated phosphorylation of Gli3S664 both in vitro and in vivo. Consequently, our study underscores the pivotal role of the SRPK1-p-Gli3S664 axis in ESCC metastasis and suggests DHA as a promising candidate for preventing ESCC metastasis by targeting this axis.