Pachyonychia Congenita: A Spectrum of <scp>KRT</scp>6a Mutations in Australian Patients

Forrest, Charlotte E.; Casey, Genevieve; Mordaunt, Dylan; Gordon, Lynne Thomas

doi:10.1111/pde.12841

Cited by 21 publications

(13 citation statements)

References 7 publications

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“…Keratin 6A is a family member of type II keratin proteins, biologically KRT6A could lead to epidermalization of squamous epithelium, 6,7 and KRT6A plays an important role in EMT in nasopharyngeal carcinoma, 6 KRT6A mutation plays an important role in pachyonychia congenita and could serve as a diagnosis marker. [7][8][9] In present study, the in vitro KRT6A silencing model was constructed to investigate the biological role of KRT6A. Our data indicate that KRT6A knockdown could significantly undermine the cancer cells proliferation and migration; moreover, KRT6A was involved with CSC transformation and EMT in LUAD.…”

Section: Introductionmentioning

confidence: 99%

KRT6A Promotes EMT and Cancer Stem Cell Transformation in Lung Adenocarcinoma

Yang

Zhang

et al. 2020

Technol Cancer Res Treat

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Aim: Keratin 6A is a type II cytokeratin which is important in forming nail bed, filiform papillae, the epithelial lining of oral mucosa, and esophagus; recently, keratin 6A was found hyperexpressed in different types of cancer. But, the biological function of keratin 6A in lung adenocarcinoma still remains unclear. Therefore, in current study, we investigated the biological role of keratin 6A in lung adenocarcinoma. Methods: By utilizing The Cancer Genome Atlas database, we investigated the expression profile of keratin 6A and its relationship with other clinical parameters in lung adenocarcinoma. The biological function of keratin 6A in lung adenocarcinoma was also investigated by using A549 and PC-9 lung cancer cell lines in vitro. Results: Our data indicate that, compared with normal lung tissue samples, keratin 6A was hyperexpressed in lung adenocarcinoma. Moreover, keratin 6A hyperexpression was positively correlated with lymph node positive and aggressive tumor T stage. Keratin 6A knockdown inhibited the cell proliferation, migration, and colony formation ability but not cell death in lung adenocarcinoma cells. In addition, we found keratin 6A exerted its phenotype via promoting cancer stem cells (CXCR4high/CD133high) transformation and epithelial–mesenchymal transition. Conclusion: In conclusion, current study suggests that hyperexpressed keratin 6A in lung adenocarcinoma promotes lung cancer proliferation and metastasis via epithelial–mesenchymal transition and cancer stem cells transformation.

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Section: Introductionmentioning

confidence: 99%

KRT6A Promotes EMT and Cancer Stem Cell Transformation in Lung Adenocarcinoma

Yang

Zhang

et al. 2020

Technol Cancer Res Treat

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“…A previous study demonstrated that keratin may also function to regulate cell growth and apoptosis as well as protecting cells from impairment and non-mechanical stress (25). Keratin 6A (KRT6A) is a family member of keratin proteins and can lead to epidermalization of squamous epithelium (26,27). KRT6A is a biomarker that is unique to squamous cells (28), while NPC is an undifferentiated squamous cell carcinoma (29,30).…”

Section: Introductionmentioning

confidence: 99%

Keratin 6A gene silencing suppresses cell invasion and metastasis of nasopharyngeal carcinoma via the β‑catenin cascade

Chen

Shan

2019

Mol Med Report

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Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. This study aimed to study the mechanisms of ectopic keratin 6A (KRT6A) in NPC. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to detect KRT6A levels in NPC cell lines (C666-1, 5-8F and SUNE-1) and a nasopharyngeal epithelial cell line (NP69, as a control). After SUNE-1 NPC cells had been silenced by KRT6A, cell viability, metastasis and invasion were determined using Cell Counting Kit-8, wound healing and Transwell assays, respectively. KRT6A levels, metastasis-associated factors and the Wnt/β-catenin pathway were measured using RT-qPCR and western blotting. It was demonstrated that KRT6A was upregulated in all detected NPC cells, among which KRT6A was the highest in SUNE-1 cells. In SUNE-1 cells, cell viability was inhibited at 24 and 48 h, and that cell metastasis and invasion were demonstrated to be suppressed by KRT6A silencing. Both the mRNA and protein levels of KRT6A, matrix metalloproteinase (MMP)-2, MMP-9, β-catenin, lymphoid enhancer binding factor 1 and T-cell specific factor 4 were reduced in the small interfering (si)KRT6A group. However, the results demonstrated that the levels of epithelial-cadherin and tissue inhibitor of metalloproteinase-2 (TIMP-2) were promoted in the siKRT6A group. The activation of the Wnt/β-catenin pathway by lithium chloride reversed the effect of si-KRT6A by modulating the expression of MMP-2/9 and TIMP2. It was observed that KRT6A silencing suppressed cell invasion and metastasis of NPC via the β-catenin cascade. Together these results provide important insights into a novel approach for the diagnosis and treatment of NPC.

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“…Other frequently reported features of PC‐6a are oral leukokeratosis and palmoplantar blisters, while pilosebaceous/epidermal cysts are predominantly found in PC‐6b or PC‐17 2 . However, our patient rarely showed generalized vesicles/bullae with PC‐6a 2,3 . These atypical manifestations could lead to a misdiagnosis of epidermolysis bullosa.…”

Section: Discussionmentioning

confidence: 59%