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Signaling Pathways of Skin Tumors

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 5393

Special Issue Editor

Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Interests: skin cancer; dermatopathology; skin surgery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The skin is a highly sophisticated barrier tissue that protects the interior of the body against continuous external injuries. The skin is composed of the epidermis, dermis, subcutaneous fat, hair follicles, sweat glands, blood vessels, and nerve fibers, all of which have the potency to develop skin tumors. Recent advances in molecular science have yielded molecular-targeted drugs, and some have been used for the treatment of skin tumors (e.g., BRAF-inhibitors for melanoma). However, new therapeutic targets are still demanded to develop better drugs.

This Special Issue of IJMS welcomes scientific contributions and critical reviews analyzing the signaling pathways of skin tumors. In many of skin tumors, dysregulated signaling pathways will be responsible for tumorigenesis, malignant transformation, tumor proliferation, tumor progression, and tumor metastasis. Potential topics include but are not limited to the following:

  • Wnt signaling;
  • Sonic Hedgehog signaling;
  • BMP signaling;
  • Notch signaling;
  • TGF signaling;
  • AKT/mTOR signaling;
  • Hippo-YAP signaling.

Dr. Takamichi Ito
Guest Editor

Manuscript Submission Information

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Keywords

  • signaling pathway
  • transcription factor
  • metastasis
  • tumorigenesis
  • epithelial-to-mesenchymal transition
  • angiogenesis

Published Papers (2 papers)

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14 pages, 8284 KiB  
Article
TBX1 and Basal Cell Carcinoma: Expression and Interactions with Gli2 and Dvl2 Signaling
by Cinzia Caprio, Silvia Varricchio, Marchesa Bilio, Federica Feo, Rosa Ferrentino, Daniela Russo, Stefania Staibano, Daniela Alfano, Caterina Missero, Gennaro Ilardi and Antonio Baldini
Int. J. Mol. Sci. 2020, 21(2), 607; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020607 - 17 Jan 2020
Cited by 7 | Viewed by 2516
Abstract
Early events of basal cell carcinoma (BCC) tumorigenesis are triggered by inappropriate activation of SHH signaling, via the loss of Patched1 (Ptch1) or by activating mutations of Smoothened (Smo). TBX1 is a key regulator of pharyngeal development, mainly through [...] Read more.
Early events of basal cell carcinoma (BCC) tumorigenesis are triggered by inappropriate activation of SHH signaling, via the loss of Patched1 (Ptch1) or by activating mutations of Smoothened (Smo). TBX1 is a key regulator of pharyngeal development, mainly through expression in multipotent progenitor cells of the cardiopharyngeal lineage. This transcription factor is connected to several major signaling systems, such as FGF, WNT, and SHH, and it has been linked to cell proliferation and to the regulation of cell shape and cell dynamics. Here, we show that TBX1 was expressed in all of the 51 BCC samples that we have tested, while in healthy human skin it was only expressed in the hair follicle. Signal intensity and distribution was heterogeneous among tumor samples. Experiments performed on a cellular model of mouse BCC showed that Tbx1 is downstream to GLI2, a factor in the SHH signaling, and that, in turn, it regulates the expression of Dvl2, which encodes an adaptor protein that is necessary for the transduction of WNT signaling. Consistently, Tbx1 depletion in the cellular model significantly reduced cell migration. These results suggest that TBX1 is part of a core transcription network that promotes BCC tumorigenesis. Full article
(This article belongs to the Special Issue Signaling Pathways of Skin Tumors)
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13 pages, 10180 KiB  
Article
Intra- and Inter-Tumor BRAF Heterogeneity in Acral Melanoma: An Immunohistochemical Analysis
by Takamichi Ito, Yumiko Kaku-Ito, Maho Murata, Toshio Ichiki, Yuki Kuma, Yuka Tanaka, Taketoshi Ide, Fumitaka Ohno, Maiko Wada-Ohno, Yuichi Yamada, Yoshinao Oda and Masutaka Furue
Int. J. Mol. Sci. 2019, 20(24), 6191; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20246191 - 08 Dec 2019
Cited by 16 | Viewed by 2577
Abstract
The current development of BRAF inhibitors has revolutionized the treatment of unresectable melanoma. As the potential heterogeneity of BRAF mutations in melanoma has been reported, accurate detection of BRAF mutations are important. However, the genetic heterogeneity of acral melanoma—a distinct type of melanoma [...] Read more.
The current development of BRAF inhibitors has revolutionized the treatment of unresectable melanoma. As the potential heterogeneity of BRAF mutations in melanoma has been reported, accurate detection of BRAF mutations are important. However, the genetic heterogeneity of acral melanoma—a distinct type of melanoma with a unique genetic background—has not fully been investigated. We conducted a retrospective review of our acral melanoma patients. Of the 196 patients with acral melanoma, we retrieved 31 pairs of primary and matched metastatic melanomas. We immunostained the 31 pairs with VE1, a BRAFV600E-mutation-specific monoclonal antibody. Immunohistochemistry with VE1 showed a high degree of sensitivity and specificity for detecting BRAFV600E mutations compared with the real-time polymerase chain reaction method. A total of nine primary (29.0%) and eight metastatic (25.8%) acral melanomas were positive for VE1. In three patients (9.7%), we observed a discordance of VE1 staining between the primary and metastatic lesions. Of note, VE1 immunohistochemical staining revealed a remarkable degree of intra-tumor genetic heterogeneity in acral melanoma. Our study reveals that VE1 immunostaining is a useful ancillary method for detecting BRAFV600E mutations in acral melanoma and allows for a clear visualization of intra- and inter-tumor BRAF heterogeneity. Full article
(This article belongs to the Special Issue Signaling Pathways of Skin Tumors)
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