Keratin17 Promotes Tumor Growth and is Associated with Poor Prognosis in Gastric Cancer

Hu, Hao; Xu, Dafeng; Huang, Xiaoxu; Zhu, Chunchao; Xu, Jia; Zhang, Zizhen; Zhao, Gang

doi:10.7150/jca.19838

Cited by 34 publications

(36 citation statements)

References 31 publications

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“…Univariate and multivariate analyses showed that KRT17 expression, as well as lymph node metastasis and TNM stage, are independent prognostic factors for the overall survival of LAC. Our data are consistent with a recent study reporting that KRT17 promotes tumor growth and is associated with poor prognosis in gastric cancer [ 23 ]. The inhibitory effect on tumor progression was achieved by silencing KRT17 in gastric cancer cells [ 30 ].…”

Section: Discussionsupporting

confidence: 93%

“…Consistent with the RNA screening, proteomic research revealed an overexpression of KRT17 protein in malignancies [ 19 , 20 ], which was later validated by in situ transcript assay [ 21 ]. Along with more and more high-throughput discoveries on the abnormal expression of KRT17, its clinical significance was revealed in cervical squamous carcinoma [ 22 ] and gastric cancer [ 23 ]. Furthermore, the underlying mechanism by which it regulates tumor progression seems to be tissue-specific.…”

Section: Introductionmentioning

confidence: 99%

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Keratin 17 Promotes Lung Adenocarcinoma Progression by Enhancing Cell Proliferation and Invasion

Liu

Cao

et al. 2018

Med Sci Monit

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BackgroundsLung adenocarcinoma (LAC) accounts for the majority of lung cancer, which is the leading cause of cancer-related mortality worldwide. Keratin 17 (KRT17) was reported to promote the tumor development of skin tumor and oral cancer. The aim of this study was to investigate the expression and function of KRT17 in LAC.Material/MethodsImmunohistochemical staining and quantitative PCR were performed to explore the expression of KRT17 in both LAC tissues and adjacent normal liver tissues. Chi-square test, univariate analysis, and multivariate analysis were conducted to statistically evaluate the clinical significance of KRT17 in LAC. Proliferation, migration, and invasion capacities of LAC cells were assessed after overexpression or silencing KRT17.ResultsBoth the RNA and protein levels of KRT17 were up-regulated in LAC tissues compared to normal lung tissues. High expression of KRT17 was correlated with advanced TNM stage and poor overall survival. Moreover, KRT17 was identified as a novel independent prognostic factor for LAC patients. Cellular studies showed that KRT17 can enhance the proliferation, migration, and invasion capacities of LAC cells, thereby promoting tumor progression.ConclusionsHigh expression of KRT17 is frequent in LAC tissues, which promotes tumor proliferation and invasion, and is correlated with a poor overall survival. Targeting KRT17 may be a novel direction for LAC drug development.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Keratin 17 Promotes Lung Adenocarcinoma Progression by Enhancing Cell Proliferation and Invasion

Liu

Cao

et al. 2018

Med Sci Monit

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“…Keratins are components of the cytoskeleton and play a major role in cell protection and structural support. Keratin KRT17, belonging to type I keratin, was regenerated and highly expressed in many cancers [ 38 ], including gastric cancer [ 39 ], cervical cancer [ 40 ], oral squamous cell carcinoma [ 41 ], and breast cancer [ 42 ]. Moreover, KRT17 expression was proposed as a prognostic marker that can discriminate postoperative stage II patients with colorectal cancer with a high probability of disease recurrence, as support to available risk stratification factors [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

Rusinek

Pfeifer

Cieślicka

et al. 2020

Cancers

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Background: Telomerase reverse transcriptase promoter (TERTp) mutations are related to a worse prognosis in various malignancies, including papillary thyroid carcinoma (PTC). Since mechanisms responsible for the poorer outcome of TERTp(+) patients are still unknown, searching for molecular consequences of TERTp mutations in PTC was the aim of our study. Methods: The studied cohort consisted of 54 PTCs, among them 24 cases with distant metastases. BRAF V600E, RAS, and TERTp mutational status was evaluated in all cases. Differences in gene expression profile between TERTp(+) and TERTp(−) PTCs were examined using microarrays. The evaluation of signaling pathways and gene ontology was based on the Gene Set Enrichment Analysis. Results: Fifty-nine percent (32/54) of analyzed PTCs were positive for at least one mutation: 27 were BRAF(+), among them eight were TERTp(+), and 1 NRAS(+), whereas five other samples harbored RAS mutations. Expression of four genes significantly differed in BRAF(+)TERTp(+) and BRAF(+)TERTp(−) PTCs. Deregulation of pathways involved in key cell processes was observed. Conclusions: TERTp mutations are related to higher PTC aggressiveness. CRABP2 gene was validated as associated with TERTp mutations. However, its potential use in diagnostics or risk stratification in PTC patients needs further studies.

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“…It was found that some keratins have regulatory functions, including cell movement, cell size, proliferation, apoptosis, and cell signal transduction 12–15. In the early stage of human skin injury, expression levels of KRT17, KRT6, and KRT16 increased under the induction of inflammatory factors, and the time of wound healing was significantly shortened 16.…”

Section: Introductionmentioning

confidence: 99%

“…In a mouse model of skin basaloid tumors with Gli2 gene transfection, KRT17 gene knockout significantly inhibited tumor development and growth 17. KRT17 was also found to be overexpressed in gastric cancer,12 cervical malignancy,11 breast carcinoma,8 oral squamous cell carcinoma,18 and pancreatic cancer,19 and is associated with poor prognosis of cervical cancer, gastric cancer, and oral squamous cell carcinoma 11,12,18. However, the function of KRT17 in the pathogenesis and progression of lung cancers remains unclear.…”

Section: Introductionmentioning

confidence: 99%

<p>Overexpression of KRT17 promotes proliferation and invasion of non-small cell lung cancer and indicates poor prognosis</p>

Wang¹,

Yang²,

Lei³

et al. 2019

CMAR

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Purpose Keratin 17 (KRT17) is a 48 KDa type I intermediate filament, which is mainly expressed in epithelial basal cells. KRT17 has been shown to be overexpressed in many malignant tumors and play an important role in the occurrence and development of tumors. Therefore, this study explored the role and underlying mechanism of KRT17 in non-small cell lung cancers (NSCLC). Methods KRT17 expression and its correlations with clinicopathological factors were examined in lung cancer tissues by immunohistochemistry. The prognosis value of KRT17 in NSCLCs was retrieved from The Cancer Genome Atlas (TCGA) online databases. The expression level of KRT17 was increased or decreased by KRT17 gene transfection or small RNA interference in lung cancer cells, respectively. Further, proliferation and invasiveness of lung cancer cells were determined by cell proliferation and invasion assays, respectively. Finally, expression levels of proteins related to Wnt signaling pathways and epithelial mesenchymal transition (EMT) were detected by Western blot. Results The expression level of KRT17 in NSCLCs was significantly higher than normal lung tissues. High expression of KRT17 predicted poor prognosis of patients with NSCLCs, especially lung adenocarcinomas, and was correlated with poor differentiation and lymphatic metastasis. Overexpression of KRT17 enhanced, while KRT17 knockdown inhibited, the proliferation and invasiveness of lung cancer cells. Overexpression of KRT17 up-regulated β-catenin activity and levels of Wnt target genes, such as cyclin D1, c-Myc, and MMP7. Moreover, KRT17 promoted EMT by up-regulating Vimentin, MMP-9, and Snail expression and down-regulating E-cadherin expression. Conclusion Overexpression of KRT17 is common in NSCLCs and indicates poor prognosis. Overexpression of KRT17 enhances the proliferation and invasiveness of NSCLC cells by activating the Wnt signaling pathway and EMT process. KRT17 is a potential indicator of NSCLC progression and poor survival.

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Keratin17 Promotes Tumor Growth and is Associated with Poor Prognosis in Gastric Cancer

Cited by 34 publications

References 31 publications

Keratin 17 Promotes Lung Adenocarcinoma Progression by Enhancing Cell Proliferation and Invasion

Keratin 17 Promotes Lung Adenocarcinoma Progression by Enhancing Cell Proliferation and Invasion

TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

<p>Overexpression of KRT17 promotes proliferation and invasion of non-small cell lung cancer and indicates poor prognosis</p>

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