Interferon alpha-inducible protein 27 promotes epithelial–mesenchymal transition and induces ovarian tumorigenicity and stemness

Abstract Background Antibodies and upregulated cytokines and chemokines predate the onset of rheumatoid arthritis (RA) symptoms. We aimed to identify the pathways related to the early processes leading to RA development, as well as potential novel biomarkers, using multiple protein analyses. Methods A case-control study was conducted within the Biobank of northern Sweden. The plasma samples from 118 pre-symptomatic individuals (207 samples; median predating time 4.1 years), 79 early RA patients, and 74 matched controls were analyzed. The levels of 122 unique proteins with an acknowledged relationship to autoimmunity were analyzed using 153 antibodies and a bead-based multiplex system (FlexMap3D; Luminex Corp.). The data were analyzed using multifactorial linear regression model, random forest, and network enrichment analysis (NEA) based on the 10 most significantly differentially expressed proteins for each two-by-two group comparison, using the MSigDB collection of hallmarks. Results There was a high agreement between the different statistical methods to identify the most significant proteins. The adipogenesis and interferon alpha response hallmarks differentiated pre-symptomatic individuals from controls. These two hallmarks included proteins involved in innate immunity. Between pre-symptomatic individuals and RA patients, three hallmarks were identified as follows: apical junction, epithelial mesenchymal transition, and TGF-β signaling, including proteins suggestive of cell interaction, remodulation, and fibrosis. The adipogenesis and heme metabolism hallmarks differentiated RA patients from controls. Conclusions We confirm the importance of interferon alpha signaling and lipids in the early phases of RA development. Network enrichment analysis provides a tool for a deeper understanding of molecules involved at different phases of the disease progression.

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NUB1 and FAT10 Proteins as Potential Novel Biomarkers in Cancer: A Translational Perspective

Cells ◽

10.3390/cells10092176 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2176

Author(s):

Maria Arshad ◽

Nazefah Abdul Hamid ◽

Mun Chiang Chan ◽

Fuad Ismail ◽

Geok Chin Tan ◽

...

Keyword(s):

Disease Burden ◽

Epithelial Mesenchymal Transition ◽

Nuclear Antigen ◽

Mesenchymal Transition ◽

Damage Repair ◽

Novel Biomarkers ◽

Antigen Protein ◽

Inducible Protein ◽

Proliferating Cell ◽

Interferon Inducible Protein

Cancer increases the global disease burden substantially, but it remains a challenge to manage it. The search for novel biomarkers is essential for risk assessment, diagnosis, prognosis, prediction of treatment response, and cancer monitoring. This paper examined NEDD8 ultimate buster-1 (NUB1) and F-adjacent transcript 10 (FAT10) proteins as novel biomarkers in cancer. This literature review is based on the search of the electronic database, PubMed. NUB1 is an interferon-inducible protein that mediates apoptotic and anti-proliferative actions in cancer, while FAT10 is a ubiquitin-like modifier that promotes cancer. The upregulated expression of both NUB1 and FAT10 has been observed in various cancers. NUB1 protein binds to FAT10 non-covalently to promote FAT10 degradation. An overexpressed FAT10 stimulates nuclear factor-kappa β, activates the inflammatory pathways, and induces the proliferation of cancer. The FAT10 protein interacts with the mitotic arrest deficient 2 protein, causing chromosomal instability and breast tumourigenesis. FAT10 binds to the proliferating cell nuclear antigen protein and inhibits the DNA damage repair response. In addition, FAT10 involves epithelial–mesenchymal transition, invasion, apoptosis, and multiplication in hepatocellular carcinoma. Our knowledge about them is still limited. There is a need to further develop NUB1 and FAT10 as novel biomarkers.

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TP53I11 Suppresses Extracellular Matrix-independent Survival and Mesenchymal Transition in Mammary Epithelial Cells

10.1101/301499 ◽

2018 ◽

Author(s):

Tongqian Xiao ◽

Hai Zhang ◽

Yuanshuai Zhou ◽

Junsa Geng ◽

Zhongjuan Xu ◽

...

Keyword(s):

Extracellular Matrix ◽

Epithelial Mesenchymal Transition ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Migration And Invasion ◽

Metabolic Flexibility ◽

Mesenchymal Transition ◽

Negative Effect ◽

Inducible Protein

AbstractExtracellular matrix (ECM)-independent survival is an essential prerequisite for tumor metastasis and a hallmark of epithelial cancer stem cells and epithelial-mesenchymal transition (EMT). We found that, in MCF10A and MDA-MB-231 cells, loss of TP53I11 (Tumor Protein P53 Inducible Protein 11) enhanced the ECM-independent survival and suppressed glucose starvation induced cell death by increasing the activation of AMPK that confer cells metabolic flexibility to survive under stress conditions. We show here that, TP53I11 enhanced glycolysis and promoted proliferation of MCF10A and MDA-MB-231 cells in normal culture, but exerted negative effect on EMT, cell migration and invasion, and its overexpression suppressed tumor progression and metastasis of MDA-MB-231 cells in vivo. Considering cancer cells also are confronted with the hostile environment such as nutrient scarcity during tumorigenesis and metastasis, our findings suggested that the disruption of metabolic flexibility by TP53I11 through inhibiting AMPK activation resulted in the suppression of tumorigenesis and metastasis of breast cancer.

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