Altered Expression of PRKX, WNT3 and WNT16 in Human Nodular Basal Cell Carcinoma

Carmo, Natalia Gurgel do; Sakamoto, Luís Carlos; Pogue, Robert; Mascarenhas, Cintia do Couto; Passos, Simone Karst; Felipe, Maria Sueli Soares; Andrade, Rosângela Vieira de

doi:10.21873/anticanres.11002

Cited by 11 publications

(8 citation statements)

References 37 publications

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“…In addition to hair‐loss disorders, the SHG and bulge are of particular clinical relevance because they may give rise to at least some basal cell carcinoma (BCC) in human skin, and dysregulated Wnt signalling has also been implicated in BCC pathobiology . Clinically, this renders a systematic examination of Wnt signalling in these key epithelial progenitor cell compartments of human HFs important also from an oncological perspective.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen–anagen transformation

Hawkshaw

Hardman

Alam³

et al. 2019

Br J Dermatol

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Summary Background The signals that induce anagen (growth) in ‘quiescent’ human telogen hair follicles (HFs) are as yet unknown. Their identification promises better targeted therapeutic hair growth interventions. Objectives Recognizing the central role of Wnt signalling in hair biology, the aim was to delineate the differential expression of key agonists, antagonists and target genes of this pathway during the telogen‐to‐anagen transformation of human scalp HFs. Methods This differential expression was studied by in situ hybridization in human telogen and early‐anagen scalp HF sections. Results On anagen induction, gene expression of the Wnt ligands WNT3, WNT4 and WNT10B, the Wnt ligand secretion regulator WLS, and the Wnt target genes AXIN2 and LEF1, is significantly increased within the secondary hair germ and the dermal papilla. Conversely, expression of the secreted Wnt inhibitor SFRP1 (secreted frizzled‐related protein 1) is reduced. Human epithelial HF stem cells upregulate WNT4 and WNT10A expression, suggesting that these Wnt agonists are important for stem cell activation. Conclusions We provide the first evidence that key changes in Wnt signalling that drive murine anagen induction also occur in human scalp HFs, yet with notable differences. This provides a rational basis for Wnt‐targeting therapeutic interventions to manipulate human hair growth disorders. What's already known about this topic? Upregulation of Wnt agonists and downregulation of Wnt antagonists in the secondary hair germ and/or dermal papilla drives hair growth (anagen) induction in mice. Autocrine Wnt signalling in murine epithelial hair follicle stem cells is required to maintain their stem cell function. Reduction of Wnt ligands or increased expression of Wnt antagonists induces dysregulation of the murine hair follicle cycle and causes alopecia. What does this study add? This study demonstrates for the first time that key Wnt pathway regulatory agonists, antagonists and target genes, are expressed in the human telogen‐to‐early‐anagen transformation. On human anagen induction the Wnt ligands WNT3, WNT4 and WNT10B are increased in the regenerating epithelium, whereas the Wnt antagonist, SFRP1 (secreted frizzled‐related protein 1), is reduced. Human anagen induction has fundamental differences in the expression of Wnt ligands compared with the murine system. What is the translational message? Regulation of these Wnt ligands permits targeted therapeutic interventions in human hair growth disorders and informs development of new drugs that promote or suppress anagen induction.

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Section: Discussionmentioning

confidence: 99%

Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen–anagen transformation

Hawkshaw

Hardman

Alam³

et al. 2019

Br J Dermatol

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“…Among various Wnts associated with the canonical Wnt/-catenin signaling pathway, Wnt3 was previously reported being frequently up-regulated in human cancers [8, 32, 33]. However, recent researches demonstrated that Wnt3 was down-regulated in some types of cancers and related to worse prognosis [34, 35]. With regards to HCC, Wnt3 expression was reported to be upregulated in human HCC compared to the adjacent peritumoral tissue [13].…”

Section: Discussionmentioning

confidence: 99%

Expression of the Wnt ligands gene family and its relationship to prognosis in hepatocellular carcinoma

Dong

Shi

2019

Cancer Cell Int

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Background The Wnt gene family members are known to participate regulating various normal and pathological processes including tumorigenesis. However, the association between Wnt ligands gene family and prognosis in hepatocellular carcinoma has not been systematically studied. Therefore, we evaluated the role of Wnt ligands gene family in hepatocellular carcinoma using publicly available data from The Cancer Genome Atlas (TCGA). Methods Clinical information and RNA-Seq mRNA expression data were derived from TCGA hepatocellular carcinoma cohort. Differences in overall survival (OS) and disease-free survival (DFS) between increased and decreased expression groups (defined by X-tile analyses) of Wnt ligands gene family were compared using Kaplan–Meier method and Cox regression model, with p-values calculated via log-rank test. Gene Set Enrichment Analysis (GSEA) was performed. Results Multivariate analysis adjusted for patient age, sex, BMI, tumor grade, and TMN stage revealed that Wnt1, Wnt3 and Wnt5B expressions were independent prognostic factors for OS and DFS (OS: HR = 0.58, P = 0.006; HR = 0.65, P = 0.03; HR = 0.56, P = 0.023, respectively; DFS: HR = 0.52, P < 0.001; HR = 1.93, P = 0.003; HR = 0.59, P = 0.011, respectively). Furthermore, expression of Wnt1 and Wnt5B was significantly associated with TMN stage (P = 0.02 and P = 0.03 for OS; P = 0.02 and P = 0.02 for DFS). GSEA showed that nucleotide excision repair was differentially enriched in Wnt1 low expression phenotype and aminoacyl trna biosynthesis and basal transcription factors were differentially enriched in Wnt5B low expression phenotype. Conclusions Our results identified associations of several Wnt ligands with prognosis of HCC patients, indicating that these genes could serve as prognostic biomarkers of HCC. Electronic supplementary material The online version of this article (10.1186/s12935-019-0743-z) contains supplementary material, which is available to authorized users.

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“…Wnt3 overexpression has been commonly identified in aggressive tumors. Carmo et al pointed out that BCC is not an aggressive tumor, therefore there may be different gene expression profiles in such tumors [ 70 ].…”

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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Altered Expression of PRKX, WNT3 and WNT16 in Human Nodular Basal Cell Carcinoma

Abstract: PRKX, WNT3 and WNT16 genes, belonging to the WNT signaling pathway, are involved in the tumorigenic process of nodular BCC.

Cited by 11 publications

References 37 publications

Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen–anagen transformation

Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen–anagen transformation

Expression of the Wnt ligands gene family and its relationship to prognosis in hepatocellular carcinoma

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

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