Hedgehog signaling keeps liver clock in check

Mazzoccoli, Gianluigi; Keshavarzian, Ali; Vinciguerra, Manlio

doi:10.1016/j.jhep.2019.02.009

Cited by 2 publications

(3 citation statements)

References 18 publications

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“…Lacking the Indian, Desert, and Sonic ligands, SMO is functionally stalled by Patched, encoded by PTCH1 . Furthermore, SMO activation upholds c-Myc expression and plays a part in hepatocarcinogenesis [46,47]. A recent study performed in liver and hepatocytes from wild type and Smo flox/flox and Alfp-Cre lines (SAC-KO) crossbreeds with PER2::LUC reporter mice evaluated time-qualified expression of Hh signaling and molecular clockwork cogs and evidenced a crucial interplay between HH and circadian pathways [46,47].…”

Section: The Biological Clock and The Oncogenic Pathways Involved mentioning

confidence: 99%

“…Furthermore, SMO activation upholds c-Myc expression and plays a part in hepatocarcinogenesis [46,47]. A recent study performed in liver and hepatocytes from wild type and Smo flox/flox and Alfp-Cre lines (SAC-KO) crossbreeds with PER2::LUC reporter mice evaluated time-qualified expression of Hh signaling and molecular clockwork cogs and evidenced a crucial interplay between HH and circadian pathways [46,47]. The expression in liver and hepatocytes of numerous Hh pathway genes ( Ihh , Ptch1 , Smo , Hhip1 , Fu , SuFu ) plus serum levels of Indian Hh oscillated with 24-h periodicity, whereas Gli proteins encoding genes fluctuated scarcely Bmal1 knock-out in hepatocytes disrupted expression of Hh pathway genes, with Gli1 and Ihh up-regulation and Ptch1 down-regulation.…”

Section: The Biological Clock and The Oncogenic Pathways Involved mentioning

confidence: 99%

“…On the other hand, SAC-KO mice showed altered clock genes’ expression, confirmed in vitro upon modulation with Gli1 and Gli3 siRNAs. In addition, in hepatocytes derived from SMO-KO mice lipid metabolism related genes were severely deranged and the Hh signaling-biological clock interplay was modulated by high fat diet or fasting in a time-of-day dependent manner, hinting GLI factors mediated cooperation in upholding hepatic lipid metabolism [46,47].…”

Section: The Biological Clock and The Oncogenic Pathways Involved mentioning

confidence: 99%

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A Role for the Biological Clock in Liver Cancer

Mazzoccoli

Miele

Marrone

et al. 2019

Cancers

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The biological clock controls at the molecular level several aspects of mammalian physiology, by regulating daily oscillations of crucial biological processes such as nutrient metabolism in the liver. Disruption of the circadian clock circuitry has recently been identified as an independent risk factor for cancer and classified as a potential group 2A carcinogen to humans. Hepatocellular carcinoma (HCC) is the prevailing histological type of primary liver cancer, one of the most important causes of cancer-related death worldwide. HCC onset and progression is related to B and C viral hepatitis, alcoholic and especially non-alcoholic fatty liver disease (NAFLD)-related milieu of fibrosis, cirrhosis, and chronic inflammation. In this review, we recapitulate the state-of-the-art knowledge on the interplay between the biological clock and the oncogenic pathways and mechanisms involved in hepatocarcinogenesis. Finally, we propose how a deeper understanding of circadian clock circuitry–cancer pathways’ crosstalk is promising for developing new strategies for HCC prevention and management.

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Section: The Biological Clock and The Oncogenic Pathways Involved mentioning

confidence: 99%

Section: The Biological Clock and The Oncogenic Pathways Involved mentioning

confidence: 99%

Section: The Biological Clock and The Oncogenic Pathways Involved mentioning

confidence: 99%

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A Role for the Biological Clock in Liver Cancer

Mazzoccoli

Miele

Marrone

et al. 2019

Cancers

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GLI3: a mediator of genetic diseases, development and cancer

Matissek

Elsawa

2020

Cell Commun Signal

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The transcription factor GLI3 is a member of the Hedgehog (Hh/HH) signaling pathway that can exist as a full length (Gli3-FL/GLI3-FL) or repressor (Gli3-R/GLI3-R) form. In response to HH activation, GLI3-FL regulates HH genes by targeting the GLI1 promoter. In the absence of HH signaling, GLI3 is phosphorylated leading to its partial degradation and the generation of GLI3-R which represses HH functions. GLI3 is also involved in tissue development, immune cell development and cancer. The absence of Gli3 in mice impaired brain and lung development and GLI3 mutations in humans are the cause of Greig cephalopolysyndactyly (GCPS) and Pallister Hall syndromes (PHS). In the immune system GLI3 regulates B, T and NK-cells and may be involved in LPS-TLR4 signaling. In addition, GLI3 was found to be upregulated in multiple cancers and was found to positively regulate cancerous behavior such as anchorage-independent growth, angiogenesis, proliferation and migration with the exception in acute myeloid leukemia (AML) and medulloblastoma where GLI plays an anti-cancerous role. Finally, GLI3 is a target of microRNA. Here, we will review the biological significance of GLI3 and discuss gaps in our understanding of this molecule.

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Hedgehog signaling keeps liver clock in check

Cited by 2 publications

References 18 publications

A Role for the Biological Clock in Liver Cancer

A Role for the Biological Clock in Liver Cancer

GLI3: a mediator of genetic diseases, development and cancer

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