A Functional and Putative Physiological Role of Calcitriol in Patched1/Smoothened Interaction

Linder, Benedikt; Weber, Susanne; Dittmann, Kai; Adamski, Jerzy; Hahn, Heidi; Uhmann, Anja

doi:10.1074/jbc.m115.646141

Cited by 18 publications

(17 citation statements)

References 50 publications

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“…The mechanism is not fully understood but it has been shown that vitamin D acts upstream of PTCH and downstream of GLI. Another argument that vitamin D represses the Hh pathway by inhibiting SMO function is that there is no inhibition of the Hh pathway in the case of SMO -null cells [ 96 ]. Thus, Uhman et al have shown that the application of calcitriol, the active form of vitamin D3, on the skin represses the development of BCC in Ptch mutant mice [ 97 ].…”

Section: Crosstalk Between Hh Signaling Pathway and Other Signalinmentioning

confidence: 99%

Recent Advances in Signaling Pathways Comprehension as Carcinogenesis Triggers in Basal Cell Carcinoma

Tampa

Georgescu

Mitran

et al. 2020

JCM

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Basal cell carcinoma (BCC) is the most common malignant skin tumor. BCC displays a different behavior compared with other neoplasms, has a slow evolution, and metastasizes very rarely, but sometimes it causes an important local destruction. Chronic ultraviolet exposure along with genetic factors are the most important risk factors involved in BCC development. Mutations in the PTCH1 gene are associated with Gorlin syndrome, an autosomal dominant disorder characterized by the occurrence of multiple BCCs, but are also the most frequent mutations observed in sporadic BCCs. PTCH1 encodes for PTCH1 protein, the most important negative regulator of the Hedgehog (Hh) pathway. There are numerous studies confirming Hh pathway involvement in BCC pathogenesis. Although Hh pathway has been intensively investigated, it remains incompletely elucidated. Recent studies on BCC tumorigenesis have shown that in addition to Hh pathway, there are other signaling pathways involved in BCC development. In this review, we present recent advances in BCC carcinogenesis.

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Section: Crosstalk Between Hh Signaling Pathway and Other Signalinmentioning

confidence: 99%

Recent Advances in Signaling Pathways Comprehension as Carcinogenesis Triggers in Basal Cell Carcinoma

Tampa

Georgescu

Mitran

et al. 2020

JCM

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“…As for most members of this family, the cargo of Ptch is not known. Later work from us and others demonstrated that Patched can act non-cell autonomously inhibit Smoothened by the secretion of endogenous sterol-like molecules, most notably (non-hydroxylated) vitamin D3 (Bijlsma et al, 2006; Linder et al, 2015; Roberts et al, 2016). …”

Section: Hedgehog Signaling In Development and Cancermentioning

confidence: 99%

Skin-Derived Vitamin D3 Protects against Basal Cell Carcinoma

Bijlsma

Roelink

2017

Journal of Investigative Dermatology

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Ultraviolet radiation in sunlight causes mutations that drive basal cell carcinomas. However, the incidence of these tumors plateaus with prolonged exposure, while the incidence of other skin cancers increases. Makarova and colleagues now show that vitamin D3 produced in the skin in response to ultraviolet radiation protects against its oncogenic effects by inhibiting Hedgehog signaling, whereas oral administration of vitamin D3 does not.

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“…Initial studies suggesting that PTC and SMO form a physical complex have been refuted, as PTC was shown to inhibit SMO sub-stoichiometrically, indicating that a catalytic mechanism must be at work [ 5 , 6 ]. The structural similarity of PTC with small molecule transporters suggests that it could function by shuttling a small regulator of SMO across the cell membrane [ 7 , 8 ]. It is a common assumption that all cells of early vertebrate embryos express at least one of the two Ptc genes and Smo , at least at low levels, and are therefore in principle competent to respond to HHs [ 9 ].…”

Section: A Brief Outline Of the Hedgehog Pathwaymentioning

confidence: 99%

Differential Cellular Responses to Hedgehog Signalling in Vertebrates—What is the Role of Competence?

Kiecker

Graham

Logan

2016

JDB

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A surprisingly small number of signalling pathways generate a plethora of cellular responses ranging from the acquisition of multiple cell fates to proliferation, differentiation, morphogenesis and cell death. These diverse responses may be due to the dose-dependent activities of signalling factors, or to intrinsic differences in the response of cells to a given signal—a phenomenon called differential cellular competence. In this review, we focus on temporal and spatial differences in competence for Hedgehog (HH) signalling, a signalling pathway that is reiteratively employed in embryos and adult organisms. We discuss the upstream signals and mechanisms that may establish differential competence for HHs in a range of different tissues. We argue that the changing competence for HH signalling provides a four-dimensional framework for the interpretation of the signal that is essential for the emergence of functional anatomy. A number of diseases—including several types of cancer—are caused by malfunctions of the HH pathway. A better understanding of what provides differential competence for this signal may reveal HH-related disease mechanisms and equip us with more specific tools to manipulate HH signalling in the clinic.

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A Functional and Putative Physiological Role of Calcitriol in Patched1/Smoothened Interaction

Cited by 18 publications

References 50 publications

Recent Advances in Signaling Pathways Comprehension as Carcinogenesis Triggers in Basal Cell Carcinoma

Recent Advances in Signaling Pathways Comprehension as Carcinogenesis Triggers in Basal Cell Carcinoma

Skin-Derived Vitamin D3 Protects against Basal Cell Carcinoma

Differential Cellular Responses to Hedgehog Signalling in Vertebrates—What is the Role of Competence?

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