Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours

Background: Plexiform neurofibromas occur commonly in individuals with neurofibromatosis type 1 (NF1) and consist of neurofibromatous change in multiple nerve fascicles. Previously, we had observed that both plexiform neurofibromas and normal cutaneous nerves expressed Hedgehogs (Hhs), which are intercellular signaling molecules and regulate growth and patterning during embryonic development, and their receptors. In the present study, we examined the expression of Gli1, a transcription factor which mediates Hh signaling to investigate the activation of Hh signaling in plexiform neurofibromas and normal cutaneous nerves. Methods: An antihuman Gli1 antibody was used with a standard immunoperoxidase technique to determine Gli1 expression in 5 specimens of plexiform neurofibromas and 5 specimens of normal cutaneous nerves. Results: Our results showed Gli1 expression in S-100-positive tumor cells within the involved nerve fascicles in plexiform neurofibromas but not in control normal skins. Conclusions: Our findings indicate that the Hh signaling pathway is activated in plexiform neurofibromas.

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“…As reported previously [5], cytoplasmic localization of Gli1 was observed on tumor cells of BCCs (fig. 1a).…”

Section: Resultssupporting

confidence: 65%

“…Gli1 is also expressed in several tumors including basal cell carcinomas (BCCs), medulloblastomas and sarcomas. Furthermore, overexpression of Gli1 is sufficient to induce the development of BCCs [5]. …”

Section: Introductionmentioning

confidence: 99%

Plexiform Neurofibromas Express the Transcription Factor Gli1

2004

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“…) in vivo is to misexpress them in Xenopus and zebrafish embryos [388][389][390][391], which induces the formation of tumor like structures (ITLS). ITLS's thus form as a result of genetic interference with signaling pathways altered in several cancer types including basal cell carcinoma, lung cancer, leukemia, melanoma, and rhabdomysarcoma [392][393][394][395].…”

Section: Trp248mentioning

confidence: 99%

Cancer as a disorder of patterning information: computational and biophysical perspectives on the cancer problem

Moore

Walker

Levin

2017

Converg. Sci. Phys. Oncol.

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TOPICAL REVIEWCancer as a disorder of patterning information: computational and biophysical perspectives on the cancer problem IntroductionCancer is well-recognized not only as an extremely pernicious medical problem, but also as a group of phenomena deeply connected to the fundamental questions of evolution, multicellularity, pattern (disregulation, and the interplay between the genome and the environment [1,2]. Two fundamental paradigms currently divide the field. One is that cancer results from disorders of genetics: cancer cells are fundamentally broken due to genomic mutation or instability, and their clonal progeny form tumors and metastases. This view is sometimes called the SMT, somatic mutation theory [3][4][5]. A competing perspective is that of cancer as a circuit disease-a disorder of the complex biophysical, transcriptional, and epigenetic dynamics that regulate cellular state and the ability of cells to cooperate in vivo [6][7][8]. Under this view (sometimes called the tissue organization field theory or TOFT, [9,10]), cancer is akin to a traffic jam [11]-the problem is not a permanent discrete alteration within a founder cell and all of its clonal descendants, but an undesirable stable attractor in the complex network of controls that normally guides anatomical homeostasis [12].The relative merits of the two models have been discussed extensively [10,[13][14][15][16][17] AbstractThe current paradigm views cancer as arising clonally from a degradation of genetic information in single cells. A complementary perspective, originating at the dawn of modern developmental biology, is that cancer is the result of a system disorder of algorithms that normally orchestrate individual cell activities toward specific anatomical structures and away from tumorigenesis. A view of cancer as a disease of geometry focuses on the pathways that allow cells to cooperate to build and maintain large-scale anatomical patterning. Cancer may result when cells stop maintaining higher-order structures and reduce the boundary of their computational selves to a single-cell level, reverting to a unicellular lifestyle in which the rest of the organism is merely part of the environment at the expense of which all living things survive. While this view has been widely discussed, little progress has been made in providing a quantitative, mechanistic framework within which this perspective's specific and unique implications for treatment strategies can be tested and biomedically exploited. Here, we highlight two recent areas of progress which may facilitate much-needed progress on the cancer problem. First, we review the roles that endogenous bioelectrical networks, operating across many tissues in vivo, play as a medium of information processing in tumor suppression, progression, and reprogramming. Second, we provide a primer to the development of computational theory and tools for quantifying the information and causal control structures in cancer and other complex biological systems. Rigorous mathematical formalisms now exist to...

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“…Moreover, the keratin pattern of BCC resembles that of the outer root sheath of the hair follicle supporting a follicular origin for the tumor. Mutations of the Sonic hedgehog pathway have recently been shown [1, 2, 3, 4]. Abnormalities of regulatory genes of the Sonic hedgehog pathway such as ras and p53 have been reported [8, 9].…”

Section: Discussionmentioning

confidence: 99%

“…Most BCCs are sporadic. The Sonic hedgehog signaling pathway is involved in sporadic as well as hereditary BCCs, and activation of this pathway is probably a necessary if not sufficient step for tumor formation [1, 2, 3, 4]. Furthermore, the tumor’s growth is dependent on its stroma.…”

Section: Introductionmentioning

confidence: 99%

Basal Cell Carcinoma of the Earlobe after Auricular Acupuncture

Brouard¹,

Kaya²,

Vecchietti³

et al. 2002

Dermatology

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The genesis of familial and sporadic basal cell carcinomas involves activation of the Sonic hedgehog signal transduction pathway. Other known factors for the development of basal cell carcinoma are ultraviolet exposure, X-rays, race, age, gender and decreased DNA repair capacity. We here report the case of a right earlobe sporadic basal cell carcinoma in a 65-year-old woman. This case is unusual because of its earlobe localization and its association with multiple auricular acupuncture treatments. This observation suggests a connection between local traumas, which occur in the course of acupuncture treatment and ear piercing, and the genesis of basal cell carcinoma. The incidence of minor adverse events associated with acupuncture is high, but serious events are uncommon. Acupuncture is not known to date for promoting the development of tumors. This connection remains to be elucidated.

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Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours

Cited by 569 publications

References 25 publications

Plexiform Neurofibromas Express the Transcription Factor Gli1

Plexiform Neurofibromas Express the Transcription Factor Gli1

Cancer as a disorder of patterning information: computational and biophysical perspectives on the cancer problem

Basal Cell Carcinoma of the Earlobe after Auricular Acupuncture

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