scholarly journals Increased Expression of Flightless I in Cutaneous Squamous Cell Carcinoma Affects Wnt/β-Catenin Signaling Pathway

2021 ◽  
Vol 22 (24) ◽  
pp. 13203
Author(s):  
Gink N. Yang ◽  
Xanthe L. Strudwick ◽  
Claudine S. Bonder ◽  
Zlatko Kopecki ◽  
Allison J. Cowin
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Cancer Metastasis ◽  
Cellular Proliferation ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Negative Regulator ◽  
Surgical Removal

Cutaneous squamous cell carcinoma (cSCC) accounts for 25% of cutaneous malignancies diagnosed in Caucasian populations. Surgical removal in combination with radiation and chemotherapy are effective treatments for cSCC. Nevertheless, the aggressive metastatic forms of cSCC still have a relatively poor patient outcome. Studies have linked actin cytoskeletal dynamics and the Wnt/β-catenin signaling pathway as important modulators of cSCC pathogenesis. Previous studies have also shown that the actin-remodeling protein Flightless (Flii) is a negative regulator of cSCC. The aim of this study was to investigate if the functional effects of Flii on cSCC involve the Wnt/β-catenin signaling pathway. Flii knockdown was performed using siRNA in a human late stage aggressive metastatic cSCC cell line (MET-1) alongside analysis of Flii genetic murine models of 3-methylcholanthrene induced cSCC. Flii was increased in a MET-1 cSCC cell line and reducing Flii expression led to fewer PCNA positive cells and a concomitant reduction in cellular proliferation and symmetrical division. Knockdown of Flii led to decreased β-catenin and a decrease in the expression of the downstream effector of β-catenin signaling protein SOX9. 3-Methylcholanthrene (MCA)-induced cSCC in Flii overexpressing mice showed increased markers of cancer metastasis including talin and keratin-14 and a significant increase in SOX9 alongside a reduction in Flii associated protein (Flap-1). Taken together, this study demonstrates a role for Flii in regulating proteins involved in cSCC proliferation and tumor progression and suggests a potential role for Flii in aggressive metastatic cSCC.

scholarly journals T-Cadherin Is an Auxiliary Negative Regulator of EGFR Pathway Activity in Cutaneous Squamous Cell Carcinoma: Impact on Cell Motility

2012 ◽  
Vol 132 (9) ◽  
pp. 2275-2285 ◽  
Author(s):  
Emmanouil Kyriakakis ◽  
Kseniya Maslova ◽  
Maria Philippova ◽  
Dennis Pfaff ◽  
Manjunath B. Joshi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Motility ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Negative Regulator ◽  
Pathway Activity

scholarly journals Specific knockdown of HOXB7 inhibits cutaneous squamous cell carcinoma cell migration and invasion while inducing apoptosis via the Wnt/β-catenin signaling pathway

2018 ◽  
Vol 315 (5) ◽  
pp. C675-C686 ◽  
Author(s):  
Dong Gao ◽  
Hong-Quan Chen
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Cell Apoptosis ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Migration And Invasion ◽  
Cell Migration And Invasion

Metastatic cutaneous squamous cell carcinoma (CSCC) is a major cause of death associated with nonmelanoma skin cancer. The involvement of homeobox B7 ( HOXB7) in cancers has been reported. Thus, the current study intends to explore the effect of HOXB7 on CSCC and its relationship with the Wnt/β-catenin signaling pathway. Initially, microarray-based gene expression profiling of CSCC was performed, and HOXB7 was identified as an upregulated gene based on the microarray data of GSE66359 . Following this, the experimental results indicated that HOXB7 and β-catenin formed a composite, demonstrating that endogenous HOXB7 binds to β-catenin. Subsequently, CSCC cells were treated with siRNA against HOXB7 or an inhibitor of the Wnt/β-catenin signaling pathway to analyze any underlying regulatory mechanism of HOXB7 on the CSCC cells. Tumor growth involving xenografts in nude mice was also observed so as to explore whether or not HOXB7 could regulate subcutaneous tumor growth through in vivo culturing. To investigate the potential effects of HOXB7 on the Wnt/β-catenin signaling pathway, we determined the expression of HOXB7 and downstream genes of the Wnt/β-catenin signaling pathway. Notably, siRNA-mediated knockdown of HOXB7 inhibited the activation of the Wnt/β-catenin signaling pathway, thereby impeding the progression of cell viability, migration, and invasion as well as of the tumor growth, although contrarily facilitating cell apoptosis. Taken together, silencing of the HOXB7 has the mechanism of inactivating the Wnt/β-catenin signaling pathway, thereby accelerating cell apoptosis and suppressing cell migration and invasion in CSCC, which could provide a candidate target for the CSCC treatment.

scholarly journals miR-22 promotes stem cell traits via activating Wnt/β-catenin signaling in cutaneous squamous cell carcinoma

Oncogene ◽  
2021 ◽  
Author(s):  
Shukai Yuan ◽  
Peitao Zhang ◽  
Liqi Wen ◽  
Shikai Jia ◽  
Yufan Wu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cancer Metastasis ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Chemotherapy Sensitivity ◽  
Oncogenic Pathways ◽  
Chemically Induced ◽  
Xenograft Mice

AbstractEmerging evidence suggests that the cancer stem cells (CSCs) are key culprits of cancer metastasis and drug resistance. Understanding mechanisms regulating the critical oncogenic pathways and CSCs function could reveal new diagnostic and therapeutic strategies. We now report that miR-22, a miRNA critical for hair follicle stem/progenitor cell differentiation, promotes tumor initiation, progression, and metastasis by maintaining Wnt/β-catenin signaling and CSCs function. Mechanistically, we find that miR-22 facilitates β-catenin stabilization through directly repressing citrullinase PAD2. Moreover, miR-22 also relieves DKK1-mediated repression of Wnt/β-catenin signaling by targeting a FosB-DDK1 transcriptional axis. miR-22 knockout mice showed attenuated Wnt/β-catenin activity and Lgr5+ CSCs penetrance, resulting in reduced occurrence, progression, and metastasis of chemically induced cutaneous squamous cell carcinoma (cSCC). Clinically, miR-22 is abundantly expressed in human cSCC. Its expression is even further elevated in the CSCs proportion, which negatively correlates with PAD2 and FosB expression. Inhibition of miR-22 markedly suppressed cSCC progression and increased chemotherapy sensitivity in vitro and in xenograft mice. Together, our results revealed a novel miR-22-WNT-CSCs regulatory mechanism in cSCC and highlight the important clinical application prospects of miR-22, a common target molecule for Wnt/β-catenin signaling and CSCs, for patient stratification and therapeutic intervention.

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