Overexpression of Transcription Factor Ovol2 in Epidermal Progenitor Cells Results in Skin Blistering

Lee, Briana; Watanabe, Kazuhide; Haensel, Daniel; Sui, Jennifer Y.; Dai, Xing

doi:10.1016/j.jid.2017.02.985

Cited by 8 publications

(6 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, activation of OVOL2 was also detrimental to cells and accompanied with MET. For example, overexpression of Ovol2 in mouse epidermal cells led to precocious differentiation 37 and skin blistering 38 ; mutations in the promoter region of human OVOL2 that activate OVOL2 transcription have been found in congenital hereditary endothelial dystrophies 39 . Above evidences indicated that OVOL2 acts as a gatekeeper for epithelial homeostasis.…”

Section: Discussionmentioning

confidence: 99%

OVOL2 links stemness and metastasis via fine-tuning epithelial-mesenchymal transition in nasopharyngeal carcinoma

Han

Zhang

et al. 2018

Theranostics

View full text Add to dashboard Cite

Rationale: Metastasis is the leading cause of disease-related death among patients with nasopharyngeal carcinoma (NPC). Mounting evidence suggest that epithelial-mesenchymal transition (EMT) is crucial for cancer cells to acquire metastatic ability. In this study, we aim to clarify the extent to which EMT is involved in various cancer properties and identify novel markers for predicting the prognosis of NPC patients.Methods: Two cellular models derived from the same NPC cell line with distinct metastasis ability were used for microarray analysis to identify key transcriptional factors that drive metastasis. Cell migration and invasion were analyzed by wound healing and Transwell analysis. Lung metatasis was determined by tail vein injection assay. Cancer stemness was analyzed using colony formation and xenograft assay. The EMT extent was evaluated using immunoblotting, RT-qPCR and immunofluorescence of EMT markers. The value of OVOL2 in prognosis was determined by immunohistochemistry in NPC biopsies.Results: OVOL2 was the most significantly down-regulated EMT transcription factor (EMT-TF) in cellular models of NPC metatasis. Low levels of OVOL2 were associated with poor overall survival of NPC patients and the reduced expression is partly due to promoter methylation and epithelial dedifferentiation. Knockout of OVOL2 in epithelial-like NPC cells partially activates EMT program and significantly promotes cancer stemness and metastatic phenotypes. Conversely, ectopically expression of OVOL2 in mesenchymal-like cells leads to a partial transition to an epithelial phenotype and reduced malignancy. Reversing EMT by depleting ZEB1, a major target of OVOL2, does not eliminate the stemness advantage of OVOL2-deficient cells but does reduce their invasion capacity. A comparison of subpopulations at different stages of EMT revealed that the extent of EMT is positively correlated with metastasis and drug resistance; however, only the intermediate EMT state is associated with cancer stemness.Conclusion: Distinct from other canonical EMT-TFs, OVOL2 only exhibits modest effect on EMT but has a strong impact on both metastasis and tumorigenesis. Therefore, OVOL2 could serve as a prognostic indicator for cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

OVOL2 links stemness and metastasis via fine-tuning epithelial-mesenchymal transition in nasopharyngeal carcinoma

Han

Zhang

et al. 2018

Theranostics

View full text Add to dashboard Cite

show abstract

“…A partial EMT-MET-like behavior has been observed for hair follicle cell renewal from bulge stem cells, where newly generated daughters integrate in distinct cell adhesive environments as they differentiate. The transcription factor OVOL2 is required for this process (Hong et al, 2015;Lee et al, 2017). Intriguingly, Ovol2 is expressed at low levels in SOX2-GFP high and GFP low cells, while Ovol1, which regulates and may have overlapping function with Ovol2 in skin (Teng et al, 2007), is enriched 1.8 fold in P0 SOX2GFP high cells.…”

Section: Taste Placodes and Non-taste Epithelium Share A Common Krt14+ Progenitor At Mid-gestationmentioning

confidence: 99%

Onset of taste bud cell renewal starts at birth and coincides with a shift in SHH function

Golden

Larson

Shechtman

et al. 2021

eLife

View full text Add to dashboard Cite

Embryonic taste bud primordia are specified as taste placodes on the tongue surface and differentiate into the first taste receptor cells (TRCs) at birth. Throughout adult life, TRCs are continually regenerated from epithelial progenitors. Sonic hedgehog (SHH) signaling regulates TRC development and renewal, repressing taste fate embryonically, but promoting TRC differentiation in adults. Here, using mouse models, we show TRC renewal initiates at birth and coincides with onset of SHHs pro-taste function. Using transcriptional profiling to explore molecular regulators of renewal, we identified Foxa1 and Foxa2 as potential SHH target genes in lingual progenitors at birth, and show SHH overexpression in vivo alters FoxA1 and FoxA2 expression relevant to taste buds. We further bioinformatically identify genes relevant to cell adhesion and cell locomotion likely regulated by FOXA1;FOXA2, and show expression of these candidates is also altered by forced SHH expression. We present a new model where SHH promotes TRC differentiation by regulating changes in epithelial cell adhesion and migration.

show abstract

“…K8 and K18 are the keratin pair that is expressed earliest during embryonic development of the epidermis and their expressions are suppressed upon epidermal progenitor cells commitment to keratinocyte lineage [8,29]. Several transcription factors, such as p63, Ovol2 and Ctip2, have been shown to suppress K8 expression during epidermal development [6,9,30]. It has been shown that developing murine p63À/À epidermis expressed high level of K8 and failed to develop a fully mature stratified epidermis [9], suggesting that p63 may regulate epidermal development through suppressing K8 transcription.…”

Section: Regulation Of Keratin Expression During Developmentmentioning

confidence: 99%

“…Therefore, loss of function or mutation of K5 or K14 leads to defects in keratin filament formation in basal keratinocytes and thus triggers skin blistering due to fragility of the basal cell compartment in either human or mouse skin epithelium [33][34][35] (Figure 3). Additionally, it has been shown that overexpression of transcription factor Ovol2 in mouse basal keratinocytes caused reduced K5 and K14 expression, leading to a severe blistering phenotype that resembles the clinical features of EBS [30].…”

Section: Keratin Disorders and Skin Diseases 31 Epidermolysis Bullomentioning

confidence: 99%

Keratins in Skin Epidermal Development and Diseases

Zhang¹

2018

Keratin

View full text Add to dashboard Cite

Epidermal keratinocyte (KC), the major cell type in the skin epidermis, plays critical roles in forming a permeability barrier to separate internal organs from external stimuli. Keratins, constituting about 30-80% of the total protein in KCs, form the major intermediate filament cytoskeleton of KC. Keratins consist of 54 unique genes in humans and they are expressed in cell-, differentiation-and development-dependent manner. While keratin pairs K5-K14 and K1-K10 are normally associated with KCs at different cell differentiation stages, other keratin pairs such as K6-K16/K17 and K8-K18 and are usually not expressed in normal skin interfollicular epidermis, but are elevated during wounding, inflammatory skin diseases such as psoriasis or malignant conversion of KC. The expression and function of keratins are tightly regulated at both transcriptional and post-transcriptional levels. Inherited or spontaneous mutations in keratins or abnormal keratin regulations or modifications can cause KC and cutaneous tissue fragility, skin hypertrophic and inflammatory conditions or malignant transformation of KC, therefore accounting for a large number of disorders in human skin. Here we review the recent literature on how keratins are normally expressed during skin development and how mutations or misregulations of these keratins are involved in the pathogenesis of skin diseases.

show abstract

Overexpression of Transcription Factor Ovol2 in Epidermal Progenitor Cells Results in Skin Blistering

Cited by 8 publications

References 13 publications

OVOL2 links stemness and metastasis via fine-tuning epithelial-mesenchymal transition in nasopharyngeal carcinoma

OVOL2 links stemness and metastasis via fine-tuning epithelial-mesenchymal transition in nasopharyngeal carcinoma

Onset of taste bud cell renewal starts at birth and coincides with a shift in SHH function

Keratins in Skin Epidermal Development and Diseases

Contact Info

Product

Resources

About