GLI1 overexpression

Overexpressing Gli1 helped to partially counteract the suppression of HCC migration, proliferation, and EMT formation by miR-875-5p overexpression. MiR-875-5p in HCC suppresses tumors by downregulating Gli1, which supplies a novel treatment for HCC patients.

The Gli1-bFGF axis is crucial for the crosstalk between lung cancer cells and vascular cells. Targeting Gli1 is a potential therapeutic approach for NSCLC angiogenesis.

In clinical samples of ESCC, major regulatory factors of the Hedgehog pathway were up-regulated and the pathway was activated. En1 promotes the proliferation and migration of ESCC cells by regulating the Hedgehog pathway and can be used as a new potential target for targeted therapy of ESCC.

Hedgehog-Gli1-induced exosomal circ-0011536 promoted PNR via the miR-451a/VGF axis, thereby establishing that it may contribute to PDAC-associated nerve changes with activated Hedgehog signaling.

Shh signaling may be involved in the development of glioblastoma-related VTE.

Conversely, GLI1 knockdown markedly suppressed these processes. Our study uncovers a potential molecular mechanism for the occurrence of inflammatory responses and tumor progression in ACP.

Compared to the canonical Hh antagonist Vismodegib, 8e exhibited much stronger potency in suppressing the mRNA expression of Hh target genes in Hh-overactivated MEF and Vismodegib resistant MEF cells. Our study provides small molecule Gli1 degraders effectively interfering with both canonical and noncanonical Hh signaling and overcoming current Smoothened (SMO) antagonists resistance, which might pave a new avenue for developing therapeutic modalities targeting Hh/Gli1 signaling pathway.

ZSCAN18 overexpression enhanced the sensitivity of glioblastoma cells to Temozolomide...Taken together, this research uncovers the role of ZSCAN18 in regulating glioblastoma cell growth and maintenance. ZSCAN18 could be a potential glioblastoma biomarker.

Finally, in vivo experimental results showed that overexpression of LINC00641 markedly suppressed tumor growth and reduced expression of GLI1 and p-AKT in xenograft tumor mice(p < 0.05). In summary, this study highlighted that LINC00641 plays a critical role in the malignant biological progression of PTC by regulating the LINC00641/IGF2BP1/GLI1/AKT signaling pathway, which may serve as a potential therapeutic target for PTC.

GLI-1 overexpression is a risk factor for poor prognosis and could be a novel therapeutic target for AML.

Finally, we show that the integrity of two GLI binding sites in the SDF1 promoter is required for p300 recruitment. Our findings define a new role for the p300-GLI1 complex in the regulation of SDF1, providing new mechanistic insight into the molecular events controlling pancreatic cancer cells migration.

The SOX2-OT/SOX2 axis positively regulates migration of lung squamous H520 cells via Gli1-mediated EMT.

Our study suggests that UV radiation may be associated with aberrant activation of the Hh-PTCH1-Gli1 intercellular signaling pathway in BCC. The molecular mechanism of UV-related PTCH1 and Gli1 differential expression deserves more rigorous research in the future.

In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

Our study provides insight into the unique and overlapping transcriptional output of the GLI proteins in melanoma. We suggest that our findings could provide new potential targets to consider while designing melanoma-targeted therapy.

Our results provide relevant prognostic data for NSCLC patients and support further studies on the Hh pathway.

Moreover, metabolic stress after GLI1 knockdown activated the energy sensor, adenosine monophosphate-activated protein kinase, which subsequently resulted in autophagy induction. In conclusion, this study indicates that targeting GLI1 reprograms the tumor glucose metabolism to suppress breast cancer cell growth and proliferation.

Majority of the genes are overlapping targets of GLI1 and GLI2; which was expected, while GLI3 regulates a small number of separate gene targets. Conclusion In this study we have identified unique and overlapping targets of GLI1; GLI2 and GLI3 in melanoma cell lines and confirmed 12 of them by qPCR on an expanded set of melanoma cell lines, suggesting these genes are novel targets of HH-GLI signaling in melanoma.

GLI overexpression can be considered as a negative prognostic factor in AML. In addition, it may offer a novel target for therapy in AML patients in near future. Key words: AML, Gli1, poor prognosis.

MEOX2/GLI1 promote resistance to cisplatin and EGFR-TKI-based therapy in lung cancer cells, modulating EGFR/AKT/ERK signalling pathway activation, as well as inducing an aberrant epigenetic modulation of the EGFR-gene expression in human lung cancer.

We provided evidence that RA restrained the nuclear translocation of Gli1 and facilitates Gli1 degradation via proteasome pathway, reducing the malignancy of PDAC cells. These findings implicated RA as a therapeutic agent for PDAC.

We demonstrate that NNK promotes acinar-to-ductal metastasis and pancreatic intraepithelial neoplasia in rats with chronic pancreatitis, accompanied by desmoplastic reaction and Gli1 overexpression. Together, we here present evidence that NNK provokes the progression of chronic pancreatitis toward pancreatic cancer and highlight potential strategies and targets for early prevention of pancreatic cancer and its therapeutics.

Curcumin can inhibit the proliferation and metastasis of TNBC cells, EMT and characteristics of BCSC by Hedgehog/Gli1 pathway.

Finally, RSPO2 depletion was impaired NPC tumor growth in vivo animal experiments. In conclusion, the present study confirmed that RSPO2 silence inhibits the tumorigenesis of NPC via ZNRF3/Hedgehog-Gli1 signal pathway.

Our recent study showed that the inhibitors of the Shh pathway such as cyclopamine (CP), a Smothened (SMO) inhibitor, and GANT61, a Gli1 inhibitor, have modest inhibitory effects on thyroid tumor cell proliferation and tumor growth...GANT61-induced autophagy was blocked by TAK1 siRNA and the inhibitors of TAK1 (5Z-7-oxozeaenol, 5Z), JNK (SP600125), and AMPK (Compound C, CC). Inhibition of autophagy by chloroquine and 5Z and by TAK1 and Beclin-1 siRNA enhanced GANT61-induced apoptosis and its antiproliferative activity. Our study has shown that inhibition of the Shh pathway induces autophagy by activating TAK1, whereas autophagy in turn suppresses GANT61-induced apoptosis. We have uncovered a previously unrecognized role of TAK1 in Shh pathway inhibition-induced autophagy and apoptosis.

These results demonstrate that SMO loss is a characteristic of NEPC and that detecting SMO by IHC could aid pathologists in NEPC diagnosis. SMO loss may promote NEPC pathogenesis by modulating AR signaling.

Notably, the GLI1 inhibitor GANT61 and the CDK4/6 inhibitor PD 0332991 had synergistic effects in promoting Ara-c sensitivity in AML cell lines and patient samples. Collectively, our data demonstrate that GLI1 reduces drug sensitivity by regulating cell cycle through the PI3K/AKT/GSK3/CDK pathway, providing a new perspective for involving GLI1 and CDK4/6 inhibitors in relapsed/refractory (RR) patient treatment.

Moreover, IHC results showed that MVP, GLI1, and P-p70S6K1 were highly expressed and positively correlated with each other in 71 human CS tissues. Overall, our findings revealed a novel regulating mechanism for HH-independent GLI1 expression and provide a rationale for combination therapy in patients with advanced CS.

NCTD attenuates HL60 proliferation via targeting the Hedgehog/SOX2 axis.

Here we report that inhibition of the Shh pathway by Gli1 siRNA or by cyclopamine and GANT61 reduced BMI1 and SOX2 expression in SW1736 and KAT-18 cells, two anaplastic thyroid cancer cell lines...Our study provides evidence that activation of the Shh pathway leads to increased BMI1 and SOX2 expression in thyroid cancer and promotes thyroid CSC-driven tumor initiation. Targeting the Shh pathway may have therapeutic value for treating thyroid cancer and preventing recurrence.

Besides, both high expression of Rab1A and FoxM1 led to a worse prognosis than anyone low group, and both low expression of Rab1A and FoxM1 had a better prognosis than the anyone low group. Therefore, Rab1A and FoxM1 play crucial roles and could be used as clinical biomarkers in CRC.

GAL-1 promotes VM in GC through the Hh/GLI pathway, which has potential as a novel therapeutic target for treatment of VM in GC.

Finally, chromatin-capture PCR confirmed long-range co-regulation of SOCS2 and FLT3 through changes in promoter conformation. These findings define a mechanism whereby SULF2 drives HCC by stimulating formation of a GLI1-STAT3 transcriptional complex.

In conclusion, MGMT inhibition could suppress the proliferation, invasion, migration and autophagy and promote the apoptosis of PanC-1/GEM cells in vitro and in vivo. PVT1 silencing may affect the PanC-1/GEM cells through changing the MGMT expression by inhibiting the SHH/GLI signaling pathway.

This study demonstrates that the combined therapy of sodium butyrate and docetaxel additively inhibits proliferation and promotes apoptosis of A549 lung adenocarcinoma cells via suppressing Gli1 expression in vitro and in vivo. Targeting Gli1 by the combined therapy may provide new insights into the therapeutic management of patients with lung adenocarcinoma.

Moreover, the drug significantly suppressed spheroid formation in CSC221 cells overexpressing Gli1/2 or EN1 (an S2-cleaved but membrane-tethered form of human Notch1) but did not suppress spheroid formation in cells overexpressing both Gli1/2 and ∆EN1, suggesting that physciosporin suppresses colon cancer cell stemness through the Sonic hedgehog and Notch signaling pathways. Together, these results demonstrate for the first time that physciosporin is a potent inhibitor of colorectal cancer cell stemness.

Steatohepatitic hepatocellular carcinoma demonstrates a distinctive morphology and gene expression profile, phenotype of zone 3 hepatocytes, and activation of the hedgehog pathway and repression of carnitine palmitoyltransferase 2, which may be important in tumorigenesis.

A retrospective study of patients with NSCLC treated with erlotinib revealed that those with a high IHC score for GLI1 protein expression had a poorer prognosis. These results indicated that GLI1 is a key regulator for TKI sensitivity, and patients with lung cancer may benefit from the combined treatment of TKI and GLI1 inhibitor.

Our findings identify molecular mechanisms that possibly explain the high sensitivity of soft-tissue sarcomas to pazopanib and may lead to the development of predictive biomarkers and novel therapies in patients with this and other types of soft-tissue sarcomas.