GLI2 as a marker of hedgehog‐responsive cells

Grzelak, Candice Alexandra; Sigglekow, Nicholas David; McCaughan, Geoffrey W.

doi:10.1002/hep.27432

Cited by 5 publications

(3 citation statements)

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“…According to the KEEG and Go analysis results in Figure 4 , we explore the differences of this pathway in XGboost-identified ARG subpopulations, and the results show that Hedgehog signaling score is different amongst ARG subgroups ( p < 2.0e-16, Figure 8F ). As previous studies report, GLI2 is closely related to Hedgehog in regulating tumor progression [ 12 , 13 ], so GLI2 is put into further analysis. We explore the correlation between Hedgehog signaling score and drug score, and the results show that Hedgehog signaling score is positively correlated with 5-Fu (r = 0.27, p < 0.001), L-OHP-1 (r = 0.45, p < 0.001), L-OHP-2 (r = 0.26, p < 0.001) ( Figure 8G ).…”

Section: Resultsmentioning

confidence: 99%

Anoikis regulator GLI2 promotes NC cell immunity escape by TGF-β-mediated non-classic hedgehog signaling in colorectal cancer: based on artificial intelligence and big data analysis

Shanshan,

Fanfei,

Xuan

et al. 2023

Aging

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Background: Anoikis is a speed-limited procedure to inhibit tumor metastasis during epithelial-mesenchymal transition (EMT). Previous studies have explored anoikis-related genes (ARG) in predicting prognosis and distinguishing tumoral immunity in many types of cancer. However, the role of ARGs in regulating NK cell exhaustion (NKE) and in predicting chemotherapy sensitivity is not clear. Therefore, it is necessary to work on it. Methods: Gene expression profiles and clinical features are collected from TCGA and GEO, and data analysis is performed in R4.2.0. Results: The ARGs-based no-supervised learning algorithm identifies three ARG subgroups, amongst which the prognosis is different. WCGNA and Artificial intelligence (AI) are applied to construct an NKE-related drug sensitivity stratification and prognosis identification model in digestive system cancer. Pathways association analysis screens out GLI2 is a key gene in regulating NKE by non-classic Hedgehog signaling (GLI2/TGF-β/IL6). In vitro experiments show that down-regulation of GLI2 enhances the CAPE-mediated cell toxicity and accompanies with down-regulation of PD-L1, tumor-derive IL6, and snial1 whereas the expression of cleaved caspas3, cleaved caspase4, cleaved PARP, and E-cadherin are up-regulated in colorectal cancer. Co-culture experiments show that GLI2- decreased colorectal tumor cells lead to down-regulation of TIM-3 and PD1 in NK cells, which are restored by TGF-bate active protein powder. Besides, the Elisa assay shows that GLI2-decreased colorectal tumor cells lead to up-regulation of IFN-gamma in NK cells.

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Section: Resultsmentioning

confidence: 99%

Anoikis regulator GLI2 promotes NC cell immunity escape by TGF-β-mediated non-classic hedgehog signaling in colorectal cancer: based on artificial intelligence and big data analysis

Shanshan,

Fanfei,

Xuan

et al. 2023

Aging

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“…FHL2 has been reported to play a role in a variety of tumors, participating in epithelial-mesenchymal transition and stabilizing EGFR [ 68 , 69 ]. The encoded product of GLI2 is a member of the transcription factor of the Gli family, which participates in the Sonic hedgehog (Shh) signaling pathway and promotes tumor progression [ 70 , 71 ].…”

Section: Current Research Status Of Fusion Genes In Gynecologic Tumorsmentioning

confidence: 99%

Fusion genes in gynecologic tumors: the occurrence, molecular mechanism and prospect for therapy

Jiang

Xie

et al. 2021

Cell Death Dis

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Gene fusions are thought to be driver mutations in multiple cancers and are an important factor for poor patient prognosis. Most of them appear in specific cancers, thus satisfactory strategies can be developed for the precise treatment of these types of cancer. Currently, there are few targeted drugs to treat gynecologic tumors, and patients with gynecologic cancer often have a poor prognosis because of tumor progression or recurrence. With the application of massively parallel sequencing, a large number of fusion genes have been discovered in gynecologic tumors, and some fusions have been confirmed to be involved in the biological process of tumor progression. To this end, the present article reviews the current research status of all confirmed fusion genes in gynecologic tumors, including their rearrangement mechanism and frequency in ovarian cancer, endometrial cancer, endometrial stromal sarcoma, and other types of uterine tumors. We also describe the mechanisms by which fusion genes are generated and their oncogenic mechanism. Finally, we discuss the prospect of fusion genes as therapeutic targets in gynecologic tumors.

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“…A major limitation of former studies is the assumption that GLI2 + cells are ‘actively’ signaling via a canonical Hh pathway [ 14 – 18 ]. As we have previously asserted, this is a misleading assumption [ 7 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease

et al. 2017

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Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations. This study extends these observations to human liver tissue, and analyses the effect of GLI inhibition on LPC viability/gene expression. Human donor and cirrhotic liver tissue specimens were evaluated for SHH, GLI2 and Pc expression using immunofluorescence and qRT-PCR. Changes to viability and gene expression in LPCs in vitro were assessed following GLI inhibition. Identification of Pc (as a marker of canonical Hh signaling) in human cirrhosis was predominantly confined to the ductular reaction and LPCs. In contrast, GLI2 was expressed in multiple cell populations including Pc-ve endothelium, hepatocytes, and leukocytes. HSCs/myofibroblasts (>99%) expressed GLI2, with only 1.92% displaying Pc. In vitro GLI signals maintained proliferation/viability within LPCs and GLI inhibition affected the expression of genes related to stemness, hepatocyte/biliary differentiation and Hh/Wnt signaling. At least two mechanisms of GLI signaling (Pc/SMO-dependent and Pc/SMO-independent) mediate chronic liver disease pathogenesis. This may have significant ramifications for the choice of Hh inhibitor (anti-SMO or anti-GLI) suitable for clinical trials. We also postulate GLI delivers a pro-survival signal to LPCs whilst maintaining stemness.

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GLI2 as a marker of hedgehog‐responsive cells

Cited by 5 publications

References 4 publications

Anoikis regulator GLI2 promotes NC cell immunity escape by TGF-β-mediated non-classic hedgehog signaling in colorectal cancer: based on artificial intelligence and big data analysis

Anoikis regulator GLI2 promotes NC cell immunity escape by TGF-β-mediated non-classic hedgehog signaling in colorectal cancer: based on artificial intelligence and big data analysis

Fusion genes in gynecologic tumors: the occurrence, molecular mechanism and prospect for therapy

Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease

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