Downregulation of the Sonic Hedgehog/Gli pathway transcriptional target Neogenin-1 is associated with basal cell carcinoma aggressiveness

Casas, Bárbara S.; Adolphe, Christelle; Lois, Pablo; Navarrete, Nelson; Solís, Natalia; Bustamante, Eva; Gac, Patricio; Cabané, Patricio; Gallegos, Iván; Wainwright, Brandon; Palma, Verónica

doi:10.18632/oncotarget.21061

Cited by 9 publications

(5 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, when specifying the subtypes of BCC analyzed, we found the increase of strong levels of Shh immunoexpression in aggressive variants – infiltrative, mixed, and micronodular. These results agree with the data demonstrated by Casas et al [ 60 ]. By contrast, among the other subtypes of BCC, previously considered as aggressive variants, we found upregulation of Shh paralleled by downregulation of α -SMA immunoexpression in the superficial subtype of the tumor assumed to be nonaggressive.…”

Section: ⧉ Discussionsupporting

confidence: 94%

Analysis of the occurrence and distribution of primary and recurrent basal cell carcinoma of head and neck coupled to the assessment of tumor microenvironment and Sonic hedgehog signaling

Moisejenko-Goluboviča

Volkov²,

Иванова

et al. 2021

Rom J Morphol Embryol

View full text Add to dashboard Cite

Often, basal cell carcinoma (BCC) displays local aggressiveness, and when developed in the head and neck presents with deep tissue invasion and recurrence. Previous studies have pointed out the necessity of systematic assessment of primary and recurrent BCC based on a better understanding of the biology and function of its microenvironment. Although hedgehog-dependent tumor cells signaling to the underlying stroma, and vice versa , have been demonstrated to be implicated in the pathogenesis of BCC, little is known about peculiarities of the tumor microenvironment and the above-mentioned signaling in the head and neck. The occurrence and distribution of 79 primary and recurrent BCCs developed in the head and neck region were estimated. The data were coupled with the immunohistochemical assessment of type IV collagen, laminin, alpha-smooth muscle actin ( α -SMA), and Sonic hedgehog (Shh). The frequency of the mixed BCCs and the predominance of the nose and cheek region affection by primary and recurrent tumors were demonstrated. Furthermore, the increase of peritumoral and entire stromal α -SMA immunoreactivity in the mixed recurrent BCC was confirmed using statistics. We found the increase of strong levels of Shh immunoexpression in the aggressive variants of BCC – infiltrative, mixed, and micronodular. Surprisingly, we confirmed the upregulation of Shh paralleled by the downregulation of α -SMA immunoexpression in the superficial subtype of the tumor. Our results suggest the necessity of further studies assessing the nature of the tumor along with the peculiarities of signaling in BCCs of head and neck.

show abstract

Section: ⧉ Discussionsupporting

confidence: 94%

Analysis of the occurrence and distribution of primary and recurrent basal cell carcinoma of head and neck coupled to the assessment of tumor microenvironment and Sonic hedgehog signaling

Moisejenko-Goluboviča

Volkov²,

Иванова

et al. 2021

Rom J Morphol Embryol

View full text Add to dashboard Cite

show abstract

“…Furthermore, when specifying the subtypes of BCC analysed, we found the increase of strong levels of SHh expression in aggressive variantsinfiltrative, the mixed, and micronodular. These results are in agreement with the data demonstrated by Casas and colleagues(Casas et al, 2017).By contrast, among the other subtypes of BCC, previously considered as aggressive variants, we found upregulation of SHh paralleled by downregulation of α-SMA expression in the superficial subtype of the tumour assumed to be nonaggressive. This leads us to propose that SHh participates in normal and affected epidermal homeostasis, but the molecular pathway of the signalling is not completely understood.…”

supporting

confidence: 93%

Pathogenesis of Basal Carcinoma and Features of Development of Local Recurrences in Head and Neck. Summary of the Doctoral Thesis

Moisejenko-Goluboviča

View full text Add to dashboard Cite

Ultraviolet radiation is known to be a major cause of skin malignancies, including basal cell carcinoma (BCC), the most common type of skin cancer. With frequent development in the head and neck region, BCC is characterized by deep tissue invasion and recurrence, therefore, it is important to investigate clinical, dermatoscopic, and morphological criteria for different forms of BCC, as misinterpretation leads to incorrect treatment tactics, aggressive tumour progression, and recurrence. Ultraviolet radiation is not the only predisposing factor, also sunlight is important for general health and vitamin D synthesis in the skin, which deviates from optimal vitamin D levels with a tendency to develop BCC. Previous studies have highlighted the need to systematically evaluate primary and relapsing BCCs based on a better understanding of their morphological structure and the biology of a tumour microenvironment. Accumulating evidence suggests that vitamin D antagonises the transmission of Sonic Hedgehog (SHh) signals, and, therefore, plays an important protective role in BCCs development. The prevalence and characteristics of primary and recurrent head and neck BCCs were assessed in 79 subjects; dermatoscopic criteria were recognized; serum vitamin D levels and vitamin D binding protein (VDBP) expression in BCC tissues were assessed. The essential components of the basement membrane (BM) ‒ type IV collagen and laminin were evaluated immunohistochemically; a tumour cell biology and tumour microenvironment (TME) were explored by studying the expression of alpha-smooth muscle actin (α-SMA), podoplanin (PDPN), and SHh. The most frequent dermatoscopic criteria were established for all types of BCC; the impaired intergrity of the BM in BCC was confirmed; an increase in peritumoural and whole-panstromal α-SMA reactivity was confirmed in mixed and recurrent BCC. A marked increase in the level of SHh expression was observed in the aggressive variants of the BCC ‒ infiltrative, mixed, and micronodular. Vitamin D deficiency was determined in the cohort of patients with both primary and recurrent BCC of the head and neck. There was no statistically significant difference in serum vitamin D levels between men and women. Higher serum vitamin D levels were correlated with the appearance of smaller neoplasms and a more favorable disease prognosis. In smaller tumours with a favorable course, such as superficial and nodular BCC, the association between high-VDBP and low-SHh tissue expression was found, providing supportive evidence of the existence of a link between vitamin D, proteins involved in its metabolism, and SHh signaling pathway. 3.2 Health Sciences; Sub-Sector – Dermatology and Venereal Diseases. Keywords: basal cell carcinoma of the head and neck, dermatoscopy, podoplanin, collagen IV, laminin, tumour microenvironment, Sonic Hedgehog, alpha-smooth muscle actin, serum D vitamin level, vitamin D binding protein.

show abstract

“…Paraffin-embedded patient samples of NB were deparaffinated and rehydrated as described in [ 21 ]. IHC assays were proceeded by incubating the slides with primary antibodies anti-NEO1 (1:50, sc-15,337, Santa Cruz biotechnologies), anti-NTN1 (1:40, AF6419, sheep, R&D systems) and anti-PCNA (1: 100, 13–3900, mouse, Invitrogen) antibodies in 2.5% horse serum (from the Vestatin kit).…”

Section: Methodsmentioning

confidence: 99%

The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation

Villanueva

Sánchez-Gómez

Muñoz-Palma

et al. 2021

Cell Adhesion & Migration

Self Cite

View full text Add to dashboard Cite

Neuroblastoma is a highly metastatic tumor that emerges from neural crest cell progenitors. Focal Adhesion Kinase (FAK) is a regulator of cell migration that binds to the receptor Neogenin-1 and is upregulated in neuroblastoma. Here, we show that Netrin-1 ligand binding to Neogenin-1 leads to FAK autophosphorylation and integrin β1 activation in a FAK dependent manner, thus promoting neuroblastoma cell migration. Moreover, Neogenin-1, which was detected in all tumor stages and was required for neuroblastoma cell migration, was found in a complex with integrin β1, FAK, and Netrin-1. Importantly, Neogenin-1 promoted neuroblastoma metastases in an immunodeficient mouse model. Taken together, these data show that Neogenin-1 is a metastasis-promoting protein that associates with FAK, activates integrin β1 and promotes neuroblastoma cell migration.

show abstract

Downregulation of the Sonic Hedgehog/Gli pathway transcriptional target Neogenin-1 is associated with basal cell carcinoma aggressiveness

Cited by 9 publications

References 59 publications

Analysis of the occurrence and distribution of primary and recurrent basal cell carcinoma of head and neck coupled to the assessment of tumor microenvironment and Sonic hedgehog signaling

Analysis of the occurrence and distribution of primary and recurrent basal cell carcinoma of head and neck coupled to the assessment of tumor microenvironment and Sonic hedgehog signaling

Pathogenesis of Basal Carcinoma and Features of Development of Local Recurrences in Head and Neck. Summary of the Doctoral Thesis

The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation

Contact Info

Product

Resources

About