High expression of keratin 6C is associated with poor prognosis and accelerates cancer proliferation and migration by modulating epithelial–mesenchymal transition in lung adenocarcinoma

Hu, Haibo; Yang, Xiaoping; Zhou, Pei‐Xia; Yang, Xinai; Yin, Bin

doi:10.1007/s13258-019-00889-5

Cited by 16 publications

(11 citation statements)

References 34 publications

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“…It is worth noting that KRT6C is associated with poor prognosis and worse cancer outcome. 28 In comparison, two clusters of putative follicular keratinocytes appear specific to normal skin condition (Supplementary information, Fig. S4a ).…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, KRT6C overexpression is associated with poor diagnosis in cancer. 28 Paget cells are easily identified by their characteristic morphology — which have a clear cytoplasm and a peripherally positioned, hyperchromic nucleus, or by expression of an array of known biomarker genes. 5 , 7 Despite this, scRNA-seq allowed us to identify a number of genes uniquely expressed in Paget cells.…”

Section: Discussionmentioning

confidence: 99%

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The Msi1-mTOR pathway drives the pathogenesis of mammary and extramammary Paget’s disease

et al. 2020

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Mammary and extramammary Paget’s Diseases (PD) are a malignant skin cancer characterized by the appearance of Paget cells. Although easily diagnosed, its pathogenesis remains unknown. Here, single-cell RNA-sequencing identified distinct cellular states, novel biomarkers, and signaling pathways — including mTOR, associated with extramammary PD. Interestingly, we identified MSI1 ectopic overexpression in basal epithelial cells of human PD skin, and show that Msi1 overexpression in the epidermal basal layer of mice phenocopies human PD at histopathological, single-cell and molecular levels. Using this mouse model, we identified novel biomarkers of Paget-like cells that translated to human Paget cells. Furthermore, single-cell trajectory, RNA velocity and lineage-tracing analyses revealed a putative keratinocyte-to-Paget-like cell conversion, supporting the in situ transformation theory of disease pathogenesis. Mechanistically, the Msi1-mTOR pathway drives keratinocyte-Paget-like cell conversion, and suppression of mTOR signaling with Rapamycin significantly rescued the Paget-like phenotype in Msi1-overexpressing transgenic mice. Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Msi1-mTOR pathway drives the pathogenesis of mammary and extramammary Paget’s disease

et al. 2020

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“…Previous studies revealed that KRT6A silencing can suppress cell invasion and metastasis of nasopharyngeal carcinoma 37 . KRT6C was found to be closely related to the prognosis and metastasis of lung adenocarcinoma 38 . However, few studies discuss the role of them in melanoma.…”

Section: Discussionmentioning

confidence: 99%

Transcript levels of keratin 1/5/6/14/15/16/17 as potential prognostic indicators in melanoma patients

Han

Fan

et al. 2021

Sci Rep

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Keratins (KRTs), the intermediate filament-forming proteins of epithelial cells, are extensively used as diagnostic biomarkers in cancers and associated with tumorigenesis and metastasis in multiple cancers. However, the diverse expression patterns and prognostic values of KRTs in melanoma have yet to be elucidated. In the current study, we examined the transcriptional and clinical data of KRTs in patients with melanoma from GEO, TCGA, ONCOMINE, GEPIA, cBioPortal, TIMER and TISIDB databases. We found that the mRNA levels of KRT1/2/5/6/8/10/14/15/16/17 were significantly differential expressed between primary melanoma and metastatic melanoma. The expression levels of KRT1/2/5/6/10/14/15/16/17 were correlated with advanced tumor stage. Survival analysis revealed that the high transcription levels of KRT1/5/6/14/15/16/17 were associated with low overall survival in melanoma patients. GSEA analysis indicated that the most involved hallmarks pathways were P53 pathway, KRAS signaling, estrogen response early and estrogen response late. Furthermore, we found some correlations among the expression of KRTs and the infiltration of immune cells. Our study may provide novel insights for the selection of prognostic biomarkers for melanoma.

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“…Keratin J o u r n a l P r e -p r o o f 6c, also found in the OB lesions (Fig. 4), is important for epithelial-mesenchymal transition and is involved in cell migration and proliferation in lung cancer 36 . These results point towards an intriguing role of the keratins in lung fibrosis, inflammation and cancer.…”

Section: Discussionmentioning

confidence: 98%

Protein Signatures of Remodeled Airways in Transplanted Lungs with Bronchiolitis Obliterans Syndrome Obtained Using Laser-Capture Microdissection

Müller

Rosmark

Åhrman

et al. 2021

The American Journal of Pathology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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High expression of keratin 6C is associated with poor prognosis and accelerates cancer proliferation and migration by modulating epithelial–mesenchymal transition in lung adenocarcinoma

Cited by 16 publications

References 34 publications

The Msi1-mTOR pathway drives the pathogenesis of mammary and extramammary Paget’s disease

The Msi1-mTOR pathway drives the pathogenesis of mammary and extramammary Paget’s disease

Transcript levels of keratin 1/5/6/14/15/16/17 as potential prognostic indicators in melanoma patients

Protein Signatures of Remodeled Airways in Transplanted Lungs with Bronchiolitis Obliterans Syndrome Obtained Using Laser-Capture Microdissection

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