scholarly journals Silibinin Treatment Inhibits the Growth of Hedgehog Inhibitor-Resistant Basal Cell Carcinoma Cells via Targeting EGFR-MAPK-Akt and Hedgehog Signaling

2017 ◽  
Vol 93 (4) ◽  
pp. 999-1007 ◽  
Author(s):  
Arpit Dheeraj ◽  
Cynthia M. Rigby ◽  
Cindy L. O'Bryant ◽  
Chapla Agarwal ◽  
Rana P. Singh ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Hedgehog Signaling ◽  
Carcinoma Cells ◽  
Hedgehog Inhibitor

scholarly journals DDX5 Silencing Suppresses the Migration of Basal cell Carcinoma Cells by Downregulating JAK2/STAT3 Pathway

2019 ◽  
Vol 18 ◽  
pp. 153303381989225 ◽  
Author(s):  
Zhe Quan ◽  
Bei-bei Zhang ◽  
Fang Yin ◽  
Jiru Du ◽  
Yuan-ting Zhi ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Hedgehog Signaling ◽  
Human Cancer ◽  
Carcinoma Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Migration And Invasion ◽  
Stat3 Pathway

Basal cell carcinoma is driven by the aberrant activation of hedgehog signaling. DEAD (Asp-Glu-Ala-Asp) box protein 5 is frequently overexpressed in human cancer cells and associated with the tumor growth and invasion. The purpose of this study was to investigate the role of DEAD (Asp-Glu-Ala-Asp) box protein 5 in the growth, migration, and invasion of basal cell carcinoma. The role of DEAD (Asp-Glu-Ala-Asp) box protein 5 was detected by quantitative real-time polymerase chain reaction, Western blot, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay in basal cell carcinoma cells. The associations between JAK2/STAT3 pathway and DEAD (Asp-Glu-Ala-Asp) box protein 5 were analyzed in basal cell carcinoma cells. Results showed that DEAD (Asp-Glu-Ala-Asp) box protein 5 is overexpressed in basal cell carcinoma cells. DEAD (Asp-Glu-Ala-Asp) box protein 5 knockdown inhibited the migration and invasion of basal cell carcinoma cells. DEAD (Asp-Glu-Ala-Asp) box protein 5 knockdown increased the apoptosis of basal cell carcinoma cells induced by tunicamycin. Results found that DEAD (Asp-Glu-Ala-Asp) box protein 5 knockdown increased JAK2 and STAT3 expression in basal cell carcinoma cells. JAK2 inhibitor decreased STAT3 expression and abolished the inhibitory effects of DEAD (Asp-Glu-Ala-Asp) box protein 5 silencing on migration and invasion in basal cell carcinoma cells. In conclusion, these results indicate that DEAD (Asp-Glu-Ala-Asp) box protein 5 is a potential target for inhibiting basal cell carcinoma cells growth, migration, and invasion by downregulating JAK2/STAT3 pathway.

scholarly journals aPKC drives cilia-independent Hedgehog signaling to maintain basal cell carcinoma growth

2020 ◽  
Author(s):  
Tuyen T. L. Nguyen ◽  
Ung Seop Jeon ◽  
Vama Jhumkhawala ◽  
Kevin C. Tan ◽  
Vinay Kumar ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Usher Syndrome ◽  
Pathway Activity ◽  
Underlying Causes ◽  
Protein Kinase C Iota ◽  
Constitutively Active

AbstractPrimary cilia loss is a common feature of advanced cancers. While primary cilia are necessary to initiate Hedgehog (HH)-driven cancers, how HH pathway activity is maintained in advanced cancers devoid of primary cilia is unclear. Here, we find that HH-driven basal cell carcinoma (BCC) accumulate mutations in the Alström and Usher syndrome genes in advanced and SMO inhibitorresistant tumors. Loss of Alström and Usher syndrome gene expression, which are common underlying causes of deafness and blindness, suppresses ciliogenesis and HH signaling. Atypical protein kinase C iota/lambda (aPKC) is a GLI1 kinase with higher expression in advanced BCCs and we show that a constitutively active isoform drives HH pathway activity and mutually antagonizes primary cilia. Overexpression of the constitutively active aPKC variant can maintain HH pathway activity in the absence of primary cilia and can drive resistance to the SMO antagonist vismodegib regardless of cilia status. Finally, superficial BCCs display less primary cilia and higher aPKC expression, which is inversely correlated in nodular BCC subtypes. Our results suggest aPKC may serve as a biomarker for SMO inhibitor sensitivity and a target for clinical application.

scholarly journals Role of CRD-BP in the Growth of Human Basal Cell Carcinoma Cells

2014 ◽  
Vol 134 (6) ◽  
pp. 1718-1724 ◽  
Author(s):  
Felicite K. Noubissi ◽  
TaeWon Kim ◽  
Tisha N. Kawahara ◽  
William D. Aughenbaugh ◽  
Eric Berg ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Carcinoma Cells ◽  
Human Basal Cell Carcinoma

scholarly journals Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 449
Author(s):  
Luca Fania ◽  
Dario Didona ◽  
Roberto Morese ◽  
Irene Campana ◽  
Valeria Coco ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Hedgehog Signaling ◽  
Human Cancer ◽  
Local Treatment ◽  
Prevention Measures ◽  
Therapeutic Approaches ◽  
Genetic Characteristics ◽  
Novel Therapeutic

Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor can be associated with significant morbidity and cost. This review presents a literature overview of BCC from pathophysiology to novel therapeutic approaches. Several histopathological BCC subtypes with different prognostic values have been described. Dermoscopy and, more recently, reflectance confocal microscopy have largely improved BCC diagnosis. Although surgery is the first-line treatment for localized BCC, other nonsurgical local treatment options are available. BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. Notably, Hedgehog signaling inhibitors, such as vismodegib and sonidegib, are successfully used as targeted treatment for advanced or metastatic BCC. Furthermore, the implementation of prevention measures has demonstrated to be useful in the patient management.

scholarly journals Expression profile of sonic hedgehog signaling-related molecules in basal cell carcinoma

PLoS ONE ◽  
2019 ◽  
Vol 14 (11) ◽  
pp. e0225511 ◽  
Author(s):  
Hye Sung Kim ◽  
Young Sil Kim ◽  
Chul Lee ◽  
Myung Soo Shin ◽  
Jae Wang Kim ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Sonic Hedgehog ◽  
Expression Profile ◽  
Basal Cell ◽  
Hedgehog Signaling ◽  
Sonic Hedgehog Signaling

scholarly journals Spreading of Isolated Ptch Mutant Basal Cell Carcinoma Precursors Is Physiologically Suppressed and Counteracts Tumor Formation in Mice

2020 ◽  
Vol 21 (23) ◽  
pp. 9295
Author(s):  
Nadine Brandes ◽  
Slavica Hristomanova Mitkovska ◽  
Dominik Simon Botermann ◽  
Wiebke Maurer ◽  
Anna Müllen ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Hedgehog Signaling ◽  
Tumor Development ◽  
Tumor Formation ◽  
Epidermal Cells ◽  
Cellular Origin ◽  
Keratin 5 ◽  
Chemically Induced

Basal cell carcinoma (BCC) originate from Hedgehog/Patched signaling-activated epidermal stem cells. However, the chemically induced tumorigenesis of mice with a CD4Cre-mediated biallelic loss of the Hedgehog signaling repressor Patched also induces BCC formation. Here, we identified the cellular origin of CD4Cre-targeted BCC progenitors as rare Keratin 5+ epidermal cells and show that wildtype Patched offspring of these cells spread over the hair follicle/skin complex with increasing mouse age. Intriguingly, Patched mutant counterparts are undetectable in age-matched untreated skin but are getting traceable upon applying the chemical tumorigenesis protocol. Together, our data show that biallelic Patched depletion in rare Keratin 5+ epidermal cells is not sufficient to drive BCC development, because the spread of these cells is physiologically suppressed. However, bypassing the repression of Patched mutant cells, e.g., by exogenous stimuli, leads to an accumulation of BCC precursor cells and, finally, to tumor development.

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