POU5F1 Enhances the Invasiveness of Cancer Stem-Like Cells in Lung Adenocarcinoma by Upregulation of MMP-2 Expression

Xin, Yan-hong; Bian, Baishijiao; Yang, Xiaojun; Cui, Wei; Cui, Hongjuan; Cui, You‐Hong; Zhang, Xia; Xu, Chuan; Bian, Xiu‐Wu

doi:10.1371/journal.pone.0083373

Cited by 25 publications

(20 citation statements)

References 32 publications

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“…; Xin et al. ). Thus, while the present results demonstrate an important new pathway of AHR by dietary Cd, they also are consistent with the known lung carcinogenesis potential of Cd (Waalkes ).…”

Section: Discussionmentioning

confidence: 98%

Low-dose oral cadmium increases airway reactivity and lung neuronal gene expression in mice

et al. 2016

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Inhalation of cadmium (Cd) is associated with lung diseases, but less is known concerning pulmonary effects of Cd found in the diet. Cd has a decades‐long half‐life in humans and significant bioaccumulation occurs with chronic dietary intake. We exposed mice to low‐dose CdCl2 (10 mg/L in drinking water) for 20 weeks, which increased lung Cd to a level similar to that of nonoccupationally exposed adult humans. Cd‐treated mice had increased airway hyperresponsiveness to methacholine challenge, and gene expression array showed that Cd altered the abundance of 443 mRNA transcripts in mouse lung. In contrast to higher doses, low‐dose Cd did not elicit increased metallothionein transcripts in lung. To identify pathways most affected by Cd, gene set enrichment of transcripts was analyzed. Results showed that major inducible targets of low‐dose Cd were neuronal receptors represented by enriched olfactory, glutamatergic, cholinergic, and serotonergic gene sets. Olfactory receptors regulate chemosensory function and airway hypersensitivity, and these gene sets were the most enriched. Targeted metabolomics analysis showed that Cd treatment also increased metabolites in pathways of glutamatergic (glutamate), serotonergic (tryptophan), cholinergic (choline), and catecholaminergic (tyrosine) receptors in the lung tissue. Protein abundance measurements showed that the glutamate receptor GRIN2A was increased in mouse lung tissue. Together, these results show that in mice, oral low‐dose Cd increased lung Cd to levels comparable to humans, increased airway hyperresponsiveness and disrupted neuronal pathways regulating bronchial tone. Therefore, dietary Cd may promote or worsen airway hyperresponsiveness in multiple lung diseases including asthma.

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Section: Discussionmentioning

confidence: 98%

Low-dose oral cadmium increases airway reactivity and lung neuronal gene expression in mice

et al. 2016

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“…OCT4, expressed in both ES and EC cells, is tightly regulated to maintain the characteristics of pluripotent stem cells, as either high or low expression may induce differentiation [5,[7][8][9]. OCT4 is also expressed in a variety of solid tumors as well as in GCTs and is involved in tumorigenesis of cancer stem cells [10][11][12][13][14][15][16]. Therefore, deregulation and dysfunction of OCT4 may affect its oncogenic potential in a variety of cancers.…”

mentioning

confidence: 99%

The expression of the embryonic gene Cripto‐1 is regulated by OCT4 in human embryonal carcinoma NCCIT cells

Park

Han

et al. 2017

FEBS Letters

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Edited by Ned ManteiCripto-1 and OCT4, expressed in stem cells and cancers, play important roles in tumorigenesis. Here, we demonstrate that Cripto-1 expression is regulated by OCT4 in human embryonic carcinoma NCCIT cells. The endogenous expression of Cripto-1 and OCT4 is significantly reduced during differentiation. Cripto-1 expression is increased by OCT4 overexpression, but decreased by shRNA-mediated OCT4 knockdown. OCT4 overexpression significantly activates Cripto-1 transcriptional activity. A 5 0 -upstream minimal promoter sequence in the gene-encoding Cripto-1 is significantly activated by OCT4 overexpression. Mutation of the putative OCT4-binding site abolishes OCT4-mediated activation of the Cripto-1 promoter. The OCT4 transactivation domains mediate transcriptional activity of the Cripto-1 minimal promoter through direct interaction. Taken together, OCT4 plays an important role as a transcriptional activator of Cripto-1 expression in NCCIT cells.

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“…We performed a literature search to identify proteins that have been reported to affect the migratory response of MDA-MB-231 cells and selected three of these to validate our method. We chose myosin heavy chain 9 (MYH9) and POU class 5 homeobox 1 (POU5F1), which were expected to increase and decrease migration respectively upon siRNA knockdown ([ 15 ] [ 16 ] [ 17 ] [ 18 ]). Finally we chose polo-like kinase 1 (PLK1) as a ‘no migration’ control.…”

Section: Resultsmentioning

confidence: 99%

Bowhead: Bayesian modelling of cell velocity during concerted cell migration

et al. 2018

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Cell migration is a central biological process that requires fine coordination of molecular events in time and space. A deregulation of the migratory phenotype is also associated with pathological conditions including cancer where cell motility has a causal role in tumor spreading and metastasis formation. Thus cell migration is of critical and strategic importance across the complex disease spectrum as well as for the basic understanding of cell phenotype. Experimental studies of the migration of cells in monolayers are often conducted with ‘wound healing’ assays. Analysis of these assays has traditionally relied on how the wound area changes over time. However this method does not take into account the shape of the wound. Given the many options for creating a wound healing assay and the fact that wound shape invariably changes as cells migrate this is a significant flaw. Here we present a novel software package for analyzing concerted cell velocity in wound healing assays. Our method encompasses a wound detection algorithm based on cell confluency thresholding and employs a Bayesian approach in order to estimate concerted cell velocity with an associated likelihood. We have applied this method to study the effect of siRNA knockdown on the migration of a breast cancer cell line and demonstrate that cell velocity can track wound healing independently of wound shape and provides a more robust quantification with significantly higher signal to noise ratios than conventional analyses of wound area. The software presented here will enable other researchers in any field of cell biology to quantitatively analyze and track live cell migratory processes and is therefore expected to have a significant impact on the study of cell migration, including cancer relevant processes. Installation instructions, documentation and source code can be found at http://bowhead.lindinglab.science licensed under GPLv3.

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POU5F1 Enhances the Invasiveness of Cancer Stem-Like Cells in Lung Adenocarcinoma by Upregulation of MMP-2 Expression

Cited by 25 publications

References 32 publications

Low-dose oral cadmium increases airway reactivity and lung neuronal gene expression in mice

Low-dose oral cadmium increases airway reactivity and lung neuronal gene expression in mice

The expression of the embryonic gene Cripto‐1 is regulated by OCT4 in human embryonal carcinoma NCCIT cells

Bowhead: Bayesian modelling of cell velocity during concerted cell migration

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