Keratin 23 promotes telomerase reverse transcriptase expression and human colorectal cancer growth

Zhang, Rui; Zou, Kun; Yu, Wei; Guo, Wei; Gao, Yingying; Li, Jia; Li, Mei; Tai, Yidi; Huang, Wenlin; Song, Chun; Deng, Wuguo; Cui, Xiaonan

doi:10.1038/cddis.2017.339

Cited by 47 publications

(41 citation statements)

References 35 publications

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“…KRT5 and KRT23 serve as transitional markers for the tumor C population midway between tumor A and tumor D/fibroblast (mesenchymal) populations, with low expression at the endpoints of pseudotime and high expression at the midpoint. While KRT5 is associated with metastasis 29 , a recent study found that KRT23 activates CRC growth and migration, and that high KRT23 expression is prognostic of markedly shorter overall survival in CRC 33 . These findings suggest that HCT116 cells are undergoing EMT within the VMT, with each subpopulation occupying a distinct state.…”

Section: Lineage Hierarchy Reconstruction Reveals a Unique Vmt-derivementioning

confidence: 99%

AnIn VitroVascularized Micro-Tumor Model of Human Colorectal Cancer RecapitulatesIn VivoDrug Responses

Sj¹,

Movsesyan²,

Nguyen³

et al. 2020

Preprint

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Around 95% of anti-cancer drugs that show promise during preclinical study fail to gain FDA-approval for clinical use. This failure of the preclinical pipeline highlights the need for improved, physiologically-relevant in vitro models that can better serve as reliable drug-screening tools. The vascularized micro-tumor (VMT) is a novel three-dimensional model system that recapitulates the complex human tumor microenvironment, including perfused vasculature, within a transparent microfluidic device, allowing real-time study of drug responses and tumor-stromal interactions. Here we have validated the VMT platform for the study of colorectal cancer (CRC), the second leading cause of cancer-related deaths, by showing that gene expression, tumor heterogeneity, and treatment response in the VMT more closely model CRC tumor clinicopathology than current standard drug screening modalities, including 2-dimensional (2D) monolayer culture and 3dimensional (3D) spheroids.

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Section: Lineage Hierarchy Reconstruction Reveals a Unique Vmt-derivementioning

confidence: 99%

AnIn VitroVascularized Micro-Tumor Model of Human Colorectal Cancer RecapitulatesIn VivoDrug Responses

Sj¹,

Movsesyan²,

Nguyen³

et al. 2020

Preprint

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show abstract

“…However, in the hydrogels with the same stiffness, positive staining and cell numbers varied little with the change in the density of adhesion ligands. ALDH plays a vital role in clinical osteosarcoma metastasis[24], and CD133 is also an osteosarcoma marker of metastasis and invasion[33, 34]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Untangling the response of bone tumor cells and bone forming cells to matrix stiffness and adhesion ligand density by means of hydrogels

Jiang

Zhao

et al. 2019

Biomaterials

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How cancer cells and their anchorage-dependent normal counterparts respond to the adhesion ligand density and stiffness of the same extracellular matrix (ECM) is still not very clear. Here we investigated the effects of ECM adhesion ligand density and stiffness on bone tumor cells (osteosarcoma cells) and bone forming cells (osteoblasts) by using poly (ethylene glycol) diacrylate (PEGDA) and methacrylated gelatin (GelMA) hydrogels. By independently changing the PEGDA and GelMA content in the hydrogels, we achieved crosslinked hydrogel matrix with independently tunable stiffness (1.6, 6 and 25 kPa for 5%, 10%, 15% PEDGA, respectively) and adhesion ligand density (low, medium and high for 0.05%, 0.2%, 0.5% GelMA respectively). By using a series of biochemical and cell biological characterizations as well as in vivo studies, we confirmed that osteosarcoma and osteoblastic cells responded differently to the stiffness and adhesion ligand density within 3D ECM. When cultured within the 3D PEGDA/GelMA hydrogel matrix, osteosarcoma cells are highly dependent on the matrix stiffness via regulating the integrin-mediated focal adhesion (FA) pathway, whereas osteoblasts are highly sensitive to the matrix adhesion ligand density through regulating the integrin-mediated adherens junction (AJ) pathway. However, when seeded on the 2D surface of the hydrogels, osteosarcoma cells behaved differently and became sensitive to the matrix adhesion ligand density because they were “forced” to attach to the substrate, similar to anchorage-dependent osteoblasts. This study might provide new insights into rational design of scaffolds for generating in vitro tumor models to test anticancer therapeutics and for regenerating tissue to repair defects.

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“…Above all, it's imperative to improve the e cacy for identi cation of novel biomarkers at preliminary stage of HCC and then make therapies for HCC much more costeffective.Located on chromosome 17q21.2 and with a molecular weight of 48 kDa, KRT23 expresses a 1.65 kb mRNA and has been reported to have some function in several cancers.Protein KRT23 was highly upregulated in primary rectal cancer, which was analyzed by immunochemistry 14 . Meanwhile, KRT23 activated hTERT expression and then accelerated colorectal cancer growth 15 . In prostate basal cell carcinoma, KRT23 was recognized to be overexpressed 16 .…”

Section: Discussionmentioning

confidence: 99%

KRT23 Acts as an Oncogene in Hepatocellular Carcinoma by Regulating P21 via PI3K/AKT/GSK3β Pathway

Guo¹,

Ma²,

Wang³

et al. 2020

Preprint

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Background:Hepatocellular carcinoma (HCC) is a leading cancer worldwide for which diagnosis, treatment and progression are largely unknown. Keratin23 is a potential biomarker forHCC development; however, regulatory mechanisms underlying its expression remain unclear. Inthis research we explored the expression and effect of KRT23 underlying HCC development. Materials and methods:GEPIA was applied to analyze the expression of KRT23 in HCC samples and Kaplan-Merier survival analysis for patients’ prognosis. Next, IHC was further conducted for confirming its expression in HCC tissues. Meanwhile qRT-PCR and western blot analysis were applied to examine the expression of KRT23 on both mRNA and protein level in HCC cell lines compared with immortal hepatocyte LO2. Cell experiments including MTT assay, apoptosis analysis, cell cycle assay and clone formation assay were conducted for cell proliferation while transwell assay and scratch test for metastasis in vitro. Moreover, xenograft tumors in nude mice were further conducted for verification in vivo. As for mechanism in depth, immunofluorescence and western blot were operated to explore the effect of KRT23 on EMT and PI3K/AKT/GSK3βsignaling pathway. Furthermore, Co-immunoprecipitation was applied for interaction between KRT23 and P21. Functional rescue experiments were conducted to further testify their mutual effect.Results:For this research, we discovered the high expression of KRT23 in HCC samples and cell lines. Functionally, KRT23 knockdown reduced cell proliferation and metastasis in vitro and vivo. Furthermore, KRT23 participated in EMT progression and interacted with P21 to mediate PI3K/AKT/GSK3βpathway in HCC development.Conclusion:To summarize, KRT23 accelerated HCC proliferation and metastasis by regulating P21 via PI3K/AKT/GSK3βpathway.

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Keratin 23 promotes telomerase reverse transcriptase expression and human colorectal cancer growth

Cited by 47 publications

References 35 publications

AnIn VitroVascularized Micro-Tumor Model of Human Colorectal Cancer RecapitulatesIn VivoDrug Responses

AnIn VitroVascularized Micro-Tumor Model of Human Colorectal Cancer RecapitulatesIn VivoDrug Responses

Untangling the response of bone tumor cells and bone forming cells to matrix stiffness and adhesion ligand density by means of hydrogels

KRT23 Acts as an Oncogene in Hepatocellular Carcinoma by Regulating P21 via PI3K/AKT/GSK3β Pathway

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