The crucial role of emilin 1 gene expression during progression of tumor growth

Rabajdová, Miroslava; Urban, Peter; Špaková, Ivana; Saksun, Ladislav; Dudič, Rastislav; Ostró, A; Čaprnda, Martin; Kružliak, Peter; Adamek, Mariusz; Mareková, Mária

doi:10.1007/s00432-016-2226-0

Cited by 18 publications

(15 citation statements)

References 27 publications

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“…Our PCR microarray screen suggests that at least 10 ECM-related genes are regulated by PTP4A3. The most provocative is Emilin 1, a member of the Emilin family of proteins, which binds specifically to elastin and is a key component of the ECM in tumor tissue (53,54). Previous studies demonstrated that when Emilin 1 is absent, it alters cell-ECM interactions and enriches the opportunity for migration and invasion, suggesting that Emilin 1 functions as a tumor suppressor (55).…”

Section: Discussionmentioning

confidence: 99%

A chemical genetics approach identifies PTP4A3 as a regulator of colon cancer cell adhesion

et al. 2018

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Dysregulation of the tightly controlled protein phosphorylation networks that govern cellular behavior causes cancer. The membrane-associated, intracellular protein tyrosine phosphatase PTP4A3 is overexpressed in human colorectal cancer and contributes to cell migration and invasion. To interrogate further the role of PTP4A3 in colorectal cancer cell migration and invasion, we deleted the Ptp4a3 gene from murine colorectal tumor cells. The resulting PTP4A3 cells exhibited impaired colony formation, spheroid formation, migration, and adherence compared with the paired PTP4A3 cells. We replicated these phenotypic changes using the new small-molecule, allosteric PTP4A3 inhibitor JMS-053. A related structure, JMS-038, which lacked phosphatase inhibition, displayed no cellular activity. Reduction in cell viability and colony formation by JMS-053 occurred in both mouse and human colorectal cell lines and required PTP4A3 expression. Ptp4a3 deletion increased the expression of extracellular matrix (ECM) and adhesion genes, including the tumor suppressor Emilin 1. JMS-053 also increased Emilin 1 gene expression. Moreover, The Cancer Genome Atlas genomic database revealed human colorectal tumors with high Ptp4a3 expression had low Emilin 1 expression. These chemical and biologic reagents reveal a previously unknown communication between the intracellular PTP4A3 phosphatase and the ECM and support efforts to pharmacologically target PTP4A3.-McQueeney, K. E., Salamoun, J. M., Ahn J. G., Pekic, P., Blanco, I. K., Struckman, H. L., Sharlow, E. R., Wipf, P., Lazo, J. S. A chemical genetics approach identifies PTP4A3 as a regulator of colon cancer cell adhesion.

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Section: Discussionmentioning

confidence: 99%

A chemical genetics approach identifies PTP4A3 as a regulator of colon cancer cell adhesion

et al. 2018

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“…EMILIN/Multimerins are a unique family of glycoproteins present in the extracellular matrix (Colombatti et al, 2012). Previous research demonstrated the role of EMILIN/ Multimerins in regulating tumor growth progression (Andreuzzi et al, 2018;Rabajdova et al, 2016) including the association of EMILIN3 in LGG survival rates (Zeng et al, 2018). LGG is a chronic disease characterized by tumor migration, infiltration of the brain's connectome and recurrence after conventional treatment (Delgado-Lopez et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…The recently defined elastin microfibrillar interface protein (EMILIN) and Multimerin family is characterized by a C-terminal gC1q globular domain, containing five members: EMILIN1, EMILIN2, EMILIN3, MMRN1 and MMRN2 (Colombatti et al, 2012;Schiavinato et al, 2012). These members have exerted a diverse range of function in the previous study (Capuano et al, 2019;Rabajdova et al, 2016;Schiavinato et al, 2016), which can affect cell growth, wound healing, angiogenesis, lymphangiogenesis and tumor microenvironment, etc. Notably, previous research has reported that high expression of EMILIN3 was confirmed to predict poor survival in LGG (Zeng et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Expression patterns and the prognostic value of the EMILIN/Multimerin family members in low-grade glioma

Zhao¹,

Zhang²,

Yao³

et al. 2020

PeerJ

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Managing low-grade gliomas (LGG) remains a major medical challenge due to the infiltrating nature of the tumor and failure of surgical resection to eliminate the disease. EMILIN/Multimerins contain the gC1q signature, which is involved in many tumor processes. However, the expression and prognostic value of EMILIN/Multimerins in LGG remains unclear. This study used integrated bioinformatics analysis to investigate the expression pattern, prognostic value and function of EMILIN/Multimerins in patients with LGG. We analyzed the transcription levels and prognostic value EMILIN/Multimerins in LGG using the ONCOMINE, Gene Expression Profiling Interactive Analysis (GEPIA) and UALCAN databases. The mutation and co-expression rates of neighboring genes in EMILIN/Multimerins were studied using cBioPortal. TIMER and Metascape were used to reveal the potential function of EMILIN/Multimerins in LGG. According to our analysis, most EMILIN/Multimerins were overexpressed in LGG and shared a clear association with immune cells. GEPIA analysis confirmed that high levels of EMILIN/Multimerins, not including MMRN2, were associated with a poor prognosis in disease-free survival of patients with LGG. Additionally, we discovered that EMILIN/Multimerins may regulate LGG and we found a correlation between their expression patterns and distinct pathological grades. We found that EMILIN/Multimerins serve as possible prognostic biomarkers and high-priority therapeutic targets patients with LGG.

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“…These members have exerted a diverse range of function in the previous study (Capuano et al 2019;Rabajdova et al 2016;Schiavinato et al 2016), which can affect cell growth, wound healing, angiogenesis, lymphangiogenesis and tumor microenvironment, etc. Notably, previous research has reported that high expression of EMILIN3 was confirmed to predict poor survival in…”

Section: Introductionmentioning

confidence: 99%

Peer Review #1 of "Expression patterns and the prognostic value of the EMILIN/Multimerin family members in low-grade glioma (v0.1)"

2020

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The management of Low-grade glioma (LGG) remains a challenge because of the infiltrating nature of the tumor, which cannot be cured by surgical resection. The EMILIN/Multimerins containing the gC1q signature which were involved in many processes of tumor development. However, the expression of EMILIN/Multimerins in LGG and its prognostic value remains unclear. This study investigates the expression pattern, prognostic significance and function of EMILIN/Multimerins in LGG patients based on integrated bioinformatics analysis. The transcriptional levels and prognosis of EMILIN/Multimerins in LGG were analyzed by the ONCOMINE, GEPIA and UALCAN. The EMILIN/Multimerins' mutation, co-expression neighboring genes were analyzed via cBioProtal. TIMER and Metascape were used to reveal the potential mechanism of EMILIN/Multimerins in LGG. And we found that most EMILIN/Multimerins were overexpressed in LGG and share a clear association with immune cells. GEPIA confirmed that high levels of EMILIN/Multimerins were closely correlated with poor prognosis in LGG patients, except the MMRN2 in disease-free survival (DFS). The expression of EMILIN/Multimerins was related to different pathological grades. Potential mechanisms of different EMILIN/Multimerins in regulating LGG was revealed. Our findings showed that EMILIN/Multimerins might serve as novel prognostic biomarkers and possibly be a highpriority therapeutic target for LGG patients.

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The crucial role of emilin 1 gene expression during progression of tumor growth

Abstract: Obtained results demonstrated that the suppressive role of emilin 1 is related to the grade of growing breast tumors, and associated with increased hypoxia in the tumor microenvironment followed by elevated unfolding and degradation of tissue proteins.

Cited by 18 publications

References 27 publications

A chemical genetics approach identifies PTP4A3 as a regulator of colon cancer cell adhesion

A chemical genetics approach identifies PTP4A3 as a regulator of colon cancer cell adhesion

Expression patterns and the prognostic value of the EMILIN/Multimerin family members in low-grade glioma

Peer Review #1 of "Expression patterns and the prognostic value of the EMILIN/Multimerin family members in low-grade glioma (v0.1)"

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