O-GlcNAcylation of ITGA5 facilitates the occurrence and development of colorectal cancer

Yu, Miao; Chu, Songtao; Fei, Bingyuan; Fang, Xuedong; Liu, Zhuo

doi:10.1016/j.yexcr.2019.06.009

Cited by 34 publications

(22 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Elevated NMU upregulates the expression of integrin subunits that are known to be drivers and supporters of the formation of metastases [ 47 ]. The observed correlation between the invasive potential of NMU-overexpressing clones and upregulation of integrin expression is consistent with the reported involvement of α2 [ 48 ], α5 [ 49 ], α6β4 [ 50 ], αV [ 51 ], β1 [ 52 ], β6 [ 53 ] and αVβ5 [ 54 ] integrins in subsequent steps leading to metastasis.…”

Section: Discussionsupporting

confidence: 89%

Neuromedin U induces an invasive phenotype in CRC cells expressing the NMUR2 receptor

Przygodzka

Sochacka

Soboska

et al. 2021

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Successful colorectal cancer (CRC) therapy often depends on the accurate identification of primary tumours with invasive potential. There is still a lack of identified pathological factors associated with disease recurrence that could help in making treatment decisions. Neuromedin U (NMU) is a secretory neuropeptide that was first isolated from the porcine spinal cord, and it has emerged as a novel factor involved in the tumorigenesis and/or metastasis of many types of cancers. Previously associated with processes leading to CRC cell invasiveness, NMU has the potential to be a marker of poor outcome, but it has not been extensively studied in CRC. Methods Data from The Cancer Genome Atlas (TCGA) were used to analyse NMU and NMU receptor (NMUR1 and NMUR2) expression in CRC tissues vs. normal tissues, and real-time PCR was used for NMU and NMU receptor expression analysis. NMU protein detection was performed by immunoblotting. Secreted NMU was immunoprecipitated from cell culture-conditioned media and analysed by immunoblotting and protein sequencing. DNA demethylation by 5-aza-CdR was used to analyse the regulation of NMUR1 and NMUR2 expression. NMU receptor activity was monitored by detecting calcium mobilisation in cells loaded with fluo-4, and ERK1/2 kinase activation was detected after treatment with NMU or receptor agonist. Cell migration and invasion were investigated using membrane filters. Integrin expression was evaluated by flow cytometry. Results The obtained data revealed elevated expression of NMU and NMUR2 in CRC tissue samples and variable expression in the analysed CRC cell lines. We have shown, for the first time, that NMUR2 activation induces signalling in CRC cells and that NMU increases the motility and invasiveness of NMUR2-positive CRC cells and increases prometastatic integrin receptor subunit expression. Conclusions Our results show the ability of CRC cells to respond to NMU via activation of the NMUR2 receptor, which ultimately leads to a shift in the CRC phenotype towards a more invasive phenotype.

show abstract

Section: Discussionsupporting

confidence: 89%

Neuromedin U induces an invasive phenotype in CRC cells expressing the NMUR2 receptor

Przygodzka

Sochacka

Soboska

et al. 2021

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…ITGA5 is highly expressed in oral squamous cell carcinoma [ 27 ], pancreatic cancer [ 28 ], GC [ 11 ], and colorectal cancer [ 29 ], and its high expression is negatively correlated with patient OS. Some studies revealed the prognostic role of ITGA5 in non-small cell lung cancer through bioinformatics, which resulted as an independent prognostic predictor, and the five-year survival rate of patients with high ITGA5 expression was significantly reduced [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Expression and Prognostic Analysis of Integrins in Gastric Cancer

Wang

Zhang

et al. 2020

Journal of Oncology

View full text Add to dashboard Cite

Background. Integrins are involved in the biological process of a variety of cancers, but their importance in the diagnosis and prognosis of gastric cancer (GC) is still unclear. Therefore, this study aimed at exploring the significance of ITG gene expression in GC to evaluate its diagnosis and prognosis. Methods. GEPIA data were used to evaluate the mRNA expression of ITG genes in GC patients. The prognostic value of these genes was assessed by analyzing their mRNA expression using the Kaplan–Meier curve. The biological function of ITG genes was evaluated by GC tissue sequencing combined with GSEA bioinformatics. Based on the sequencing data, ITGA5 with the largest expression difference was selected for verification, and RT-PCR was used to verify its mRNA expression level in 40 pairs of GC and normal tissues. Results. ITG (A2, A3, A4, A5, A6, A11, AE, AL, AM, AV, AX, B1, B2, B4, B5, B6, and B8) was highly expressed in GC tissues, while ITGA8 was low, compared with their expression in normal tissues. RNA-seq data shows that ITG (A2, A5, A11, AV, and B1) expression was associated with poor prognosis and overall survival. In addition, combined with the results of GC tissue mRNA sequencing, it was further found that the differentially expressed genes in the ITGs genes. ITGA5 was highly expressed in GC tissues compared with its expression in normal tissues, as evaluated by qRT–PCR ( P < 0.001 ) and ROC ( P < 0.001 , AUC (95% CI) = 0.747 (0.641–0.851)), and confirmed that ITGA5 expression was a potential diagnostic marker for GC. Bioinformatics analysis revealed that the signaling pathway involved in ITGA5 was mainly enriched in focal adhesion, ECM-receptor interaction, and PI3K-AKT and was mainly involved in biological processes such as cell adhesion, extracellular matrix, and cell migration. Conclusion. This study suggested that ITGs were associated with the diagnosis and prognosis of GC and discovered the prognostic value and biological role of ITGA5 in GC. Thus, ITGA5 might be used as a potential diagnostic marker for GC.

show abstract

“…Moreover, alpha5beta1-integrin expression is considered a significant independent prognostic factor. Experimental evidence indicates that overexpression of alpha5-integrin accelerates proliferation and suppresses apoptosis in colon cancer cells, with colon cancer cells overexpressing alpha5-integrin found to promote tumor growth in a murine xenograft tumor model[ 80 ]. In addition, blockade of alpha5-integrin inhibits cell attachment and induces apoptosis in colon cancer cells via Akt suppression[ 81 ].…”

Section: Involvement Of Tnc In Colon Cancermentioning

confidence: 99%

Involvement of integrin-activating peptides derived from tenascin-C in colon cancer progression

Fujita¹,

Suzuki²,

Fukai³

2021

WJGO

View full text Add to dashboard Cite

Tenascin-C (TNC) is an adhesion modulatory protein present in the extracellular matrix that is highly expressed in several malignancies, including colon cancer. Although TNC is considered a negative prognostic factor for cancer patients, the substantial role of the TNC molecule in colorectal carcinogenesis and its malignant progression is poorly understood. We previously found that TNC has a cryptic functional site and that a TNC peptide containing this site, termed TNIIIA2, can potently and persistently activate beta1-integrins. In contrast, the peptide FNIII14, which contains a cryptic bioactive site within the fibronectin molecule, can inactivate beta1-integrins. This review presents the role of TNC in the development of colitis-associated colorectal cancer and in the malignant progression of colon cancer, particularly the major involvement of its cryptic functional site TNIIIA2. We propose new possible prophylactic and therapeutic strategies based on inhibition of the TNIIIA2-induced beta1-integrin activation by peptide FNIII14.

show abstract

O-GlcNAcylation of ITGA5 facilitates the occurrence and development of colorectal cancer

Cited by 34 publications

References 31 publications

Neuromedin U induces an invasive phenotype in CRC cells expressing the NMUR2 receptor

Neuromedin U induces an invasive phenotype in CRC cells expressing the NMUR2 receptor

Expression and Prognostic Analysis of Integrins in Gastric Cancer

Involvement of integrin-activating peptides derived from tenascin-C in colon cancer progression

Contact Info

Product

Resources

About