A novel regulatory role for tissue transglutaminase in epithelial-mesenchymal transition in cystic fibrosis

Nyabam, Samuel; Wang, Zejing; Thibault, Thomas; Ayinde, Oluseyi; Basar, Rameeza; Marshall, Lindsay J.; Griffin, Martin

doi:10.1016/j.bbamcr.2016.05.012

Cited by 23 publications

(29 citation statements)

References 39 publications

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“…It is also well reported that TGFβ1 can specifically induce TG2 expression [26], which we have confirmed in RKO and SW480 cells. Importantly, the specific effects of TGFβ1 on TG2 induction could be blocked by a TGFβ neutralizing antibody in these two cell lines.…”

Section: Discussionsupporting

confidence: 88%

“…Treatment of SW620 and SW480 (Figure 2B and 2C) with the TG2 selective inhibitor 1-155 [24–26] also reduced the expression of TG2 and EMT markers— vimentin and FN in SW480 and SW620 cells, and the expression of transcription factors Slug and Twist 1 in SW620 cells. 1-155 treatment also enhanced expression of the epithelial marker ZO-1 in both cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, TG2 can increase the bio-availability of TGFβ1 in the ECM, increasing the potential for the release of active TGFβ1 from the large latent TGFβ1 binding complex [14]. Alternatively, active TGFβ1 crosslinked into the matrix might be necessary to enhance and stabilise the signalling potential of this growth factor as suggested by Griffin and colleagues [26]. Taken together these effects suggest a continuous loop and mechanism, in which TGFβ1 directly, or indirectly induces TG2 via ERK1/2, and TG2 via mediating activation of ERK1/2 recruits the necessary machinery for increased TGFβ1 expression and secretion, thus sustaining EMT.…”

Section: Discussionmentioning

confidence: 99%

“…CRCs were treated with the TG2 selective cell-permeable inhibitor 1-155 [26] at 1 μM. CRCs were also treated with recombinant human (rh) TGFβ1 (2.5 ng/ml) (R&D Systems, Minneapolis, UK) or mouse anti-human TGFβ neutralising antibody (R&D Systems, Minneapolis, UK).…”

Section: Methodsmentioning

confidence: 99%

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Tissue transglutaminase induces Epithelial-Mesenchymal-Transition and the acquisition of stem cell like characteristics in colorectal cancer cells

2017

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Human colon cancer cell lines (CRCs) RKO, SW480 and SW620 were investigated for TG2 involvement in tumour advancement and aggression. TG2 expression correlated with tumour advancement and expression of markers of epithelial-mesenchymal transition (EMT). The metastatic cell line SW620 showed high TG2 expression compared to the primary tumour cell lines SW480 and RKO and could form tumour spheroids under non- adherent conditions. TG2 manipulation in the CRCs by shRNA or TG2 transduction confirmed the relationship between TG2 and EMT. TGFβ1 expression in CRC cells, and its level in the cell medium and extracellular matrix was increased in primary tumour CRCs overexpressing TG2 and could regulate TG2 expression and EMT by both canonical (RKO) and non-canonical (RKO and SW480) signalling. TGFβ1 regulation was not observed in the metastatic SW620 cell line, but TG2 knockdown or inhibition in SW620 reversed EMT. In SW620, TG2 expression and EMT was associated with increased presence of nuclear β-catenin which could be mediated by association of TG2 with the Wnt signalling co-receptor LRP5. TG2 inhibition/knockdown increased interaction between β-catenin and ubiquitin shown by co-immunoprecipitation, suggesting that TG2 could be important in β-catenin regulation. β-Catenin and TG2 was also upregulated in SW620 spheroid cells enriched with cancer stem cell marker CD44 and TG2 inhibition/knockdown reduced the spheroid forming potential of SW620 cells. Our data suggests that TG2 could hold both prognostic and therapeutic significance in colon cancer.

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Section: Discussionsupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Tissue transglutaminase induces Epithelial-Mesenchymal-Transition and the acquisition of stem cell like characteristics in colorectal cancer cells

2017

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“…CF affects not only the physiological function of lungs, but also the pancreas, liver and intestines (22,28). In our study, CFTR was the hub protein in the PPI network, had the highest connectivity with 182 genes (Figure 2).…”

Section: Discussionmentioning

confidence: 59%

Weighted gene co-expression network analysis in identification of metastasis-related genes of lung squamous cell carcinoma based on the Cancer Genome Atlas database

Tian¹,

Zhao²,

Xiu³

et al. 2017

J. Thorac. Dis.

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Background: Lung squamous cell carcinoma (lung SCC) is a common type of malignancy. Its pathogenesis mechanism of tumor development is unclear. The aim of this study was to identify key genes for diagnosis biomarkers in lung SCC metastasis. Methods: We searched and downloaded mRNA expression data and clinical data from The Cancer Genome Atlas (TCGA) database to identify differences in mRNA expression of primary tumor tissues from lung SCC with and without metastasis. Gene co-expression network analysis, protein-protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and quantitative real-time polymerase chain reactions (qRT-PCR) were used to explore the biological functions of the identified dysregulated genes.Results: Four hundred and eighty-two differentially expressed genes (DEGs) were identified between lung SCC with and without metastasis. Nineteen modules were identified in lung SCC through weighted gene co-expression network analysis (WGCNA). Twenty-three DEGs and 26 DEGs were significantly enriched in the respective pink and black module. KEGG pathway analysis displayed that 26 DEGs in the black module were significantly enriched in bile secretion pathway. Forty-nine DEGs in the two gene co-expression module were used to construct PPI network. CFTR in the black module was the hub protein, had the connectivity with 182 genes. The results of qRT-PCR displayed that FIGF, SFTPD, DYNLRB2 were significantly down-regulated in the tumor samples of lung SCC with metastasis and CFTR, SCGB3A2, SSTR1, SCTR, ROPN1L had the down-regulation tendency in lung SCC with metastasis compared to lung SCC without metastasis. Conclusions: The dysregulated genes including CFTR, SCTR and FIGF might be involved in the pathology of lung SCC metastasis and could be used as potential diagnosis biomarkers or therapeutic targets for lung SCC. IntroductionLung squamous cell carcinoma (lung SCC) is a histological subtype of non-small cell lung cancer (NSCLC), which is the second most frequent type of NSCLC after lung adenocarcinoma (1). Lung SCC is a multi-step progressive disease with high rates of morbidity and mortality worldwide.The initiation of lung SCC is divided into the following five successive stages: normal bronchial epithelium, squamous metaplasia, mild-moderate dysplasia, carcinoma in situ, and invasive carcinoma (2). The prognosis of lung cancer is unfavorable, despite significant therapeutic improvements have been made in recent years. In current, there is no specific molecular targets for therapy have been identified (3), therefore, cisplatin plus gemcitabine is still the first-line treatment for lung SCC (4).Currently, the tumorigenesis mechanism of lung SCC remains unclear. Numerous published articles demonstrate that dysregulated genes are essential for initiation, progression and development of lung cancer. SMC4 (structural maintenance of chromosome 4) is over-expressed in lung adenocarcinoma tissues and its inhibition significantly suppresses the prolif...

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Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Phan

Paliogiannis

Nasrallah

et al. 2020

Cell. Mol. Life Sci.

214

152

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Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and typically lethal disease characterized by an abnormal fibrotic response involving vast areas of the lungs. Given the poor knowledge of the mechanisms underpinning IPF onset and progression, a better understanding of the cellular processes and molecular pathways involved is essential for the development of effective therapies, currently lacking. Besides a number of established IPF-associated risk factors, such as cigarette smoking, environmental factors, comorbidities, and viral infections, several other processes have been linked with this devastating disease. Apoptosis, senescence, epithelial-mesenchymal transition, endothelial-mesenchymal transition, and epithelial cell migration have been shown to play a key role in IPF-associated tissue remodeling. Moreover, molecules, such as chemokines, cytokines, growth factors, adenosine, glycosaminoglycans, non-coding RNAs, and cellular processes including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, hypoxia, and alternative polyadenylation have been linked with IPF development. Importantly, strategies targeting these processes have been investigated to modulate abnormal cellular phenotypes and maintain tissue homeostasis in the lung. This review provides an update regarding the emerging cellular and molecular mechanisms involved in the onset and progression of IPF.

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A novel regulatory role for tissue transglutaminase in epithelial-mesenchymal transition in cystic fibrosis

Cited by 23 publications

References 39 publications

Tissue transglutaminase induces Epithelial-Mesenchymal-Transition and the acquisition of stem cell like characteristics in colorectal cancer cells

Tissue transglutaminase induces Epithelial-Mesenchymal-Transition and the acquisition of stem cell like characteristics in colorectal cancer cells

Weighted gene co-expression network analysis in identification of metastasis-related genes of lung squamous cell carcinoma based on the Cancer Genome Atlas database

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

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