Breast Carcinoma Progression and Tumour Vascular Markers Related to Apoptotic Mechanisms

Rabajdová, Miroslava; Urban, Peter; Gregová, Kristína; Varga, J; Fialkovicova, Viera; Kružliak, Peter; Mareková, Mária

doi:10.1155/2014/156034

Cited by 8 publications

(8 citation statements)

References 30 publications

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“…In addition, GPM6B was profoundly expressed and coexpressed with SMC differentiation markers in embryonic SMCs, indicating that GPM6B might play a role in smooth muscle development. Previous studies have demonstrated that GPM6B is a good vascular marker in breast carcinoma and ovarian carcinoma and have shown that the expression of this protein correlates with the intensity of neovascularization during tumor growth [48][49][50], suggesting its role in tumor angiopoiesis. As SMC differentiation is a critical step in the formation of the vascular system, the essential role of GPM6B in SMC differentiation may implicate this protein as a tumor vascular marker.…”

Section: Discussionmentioning

confidence: 99%

Glycoprotein M6B Interacts with TβRI to Activate TGF-β-Smad2/3 Signaling and Promote Smooth Muscle Cell Differentiation

et al. 2018

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Smooth muscle cells (SMCs), which form the walls of blood vessels, play an important role in vascular development and the pathogenic process of vascular remodeling. However, the molecular mechanisms governing SMC differentiation remain poorly understood. Glycoprotein M6B (GPM6B) is a four‐transmembrane protein that belongs to the proteolipid protein family and is widely expressed in neurons, oligodendrocytes, and astrocytes. Previous studies have revealed that GPM6B plays a role in neuronal differentiation, myelination, and osteoblast differentiation. In the present study, we found that the GPM6B gene and protein expression levels were significantly upregulated during transforming growth factor‐β1 (TGF‐β1)‐induced SMC differentiation. The knockdown of GPM6B resulted in the downregulation of SMC‐specific marker expression and repressed the activation of Smad2/3 signaling. Moreover, GPM6B regulates SMC Differentiation by Controlling TGF‐β‐Smad2/3 Signaling. Furthermore, we demonstrated that similar to p‐Smad2/3, GPM6B was profoundly expressed and coexpressed with SMC differentiation markers in embryonic SMCs. Moreover, GPM6B can regulate the tightness between TβRI, TβRII, or Smad2/3 by directly binding to TβRI to activate Smad2/3 signaling during SMC differentiation, and activation of TGF‐β‐Smad2/3 signaling also facilitate the expression of GPM6B. Taken together, these findings demonstrate that GPM6B plays a crucial role in SMC differentiation and regulates SMC differentiation through the activation of TGF‐β‐Smad2/3 signaling via direct interactions with TβRI. This finding indicates that GPM6B is a potential target for deriving SMCs from stem cells in cardiovascular regenerative medicine. Stem Cells 2018 Stem Cells 2019;37:190–201

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Section: Discussionmentioning

confidence: 99%

Glycoprotein M6B Interacts with TβRI to Activate TGF-β-Smad2/3 Signaling and Promote Smooth Muscle Cell Differentiation

et al. 2018

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“…This indicates that high levels of TNFSF9 in TNBC (Figure 4 and Supplementary Figure 3) might inhibit CD8+TILs to reduce cytotoxicity, leading to enhanced aggressiveness of TNBC. TNFRSF21 (DR6) level is known to be increased in a grade-dependent manner in BC [69], although the functional role of TNFRSF21 in TNBC is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Serum amyloid A predisposes inflammatory tumor microenvironment in triple negative breast cancer

et al. 2019

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Acute-phase proteins (APPs) are associated with a variety of disorders such as infection, inflammatory diseases, and cancers. The signature profile of APPs in breast cancer (BC) is poorly understood. Here, we identified serum amyloid A (SAA) for proinflammatory predisposition in BC through the signature profiles of APPs, interleukin (IL) and tumor necrosis factor (TNF) superfamily using publicly available datasets of tumor samples and cell lines. Triple-negative breast cancer (TNBC) subtype highly expressed SAA1/2 compared to HER2, luminal A (LA) and luminal B (LB) subtypes. IL1A, IL1B, IL8/CXCL8, IL32 and IL27RA in IL superfamily and CD70, TNFSF9 and TNFRSF21 in TNF superfamily were highly expressed in TNBC compared to other subtypes. SAA is restrictedly regulated by nuclear factor (NF)-κB and IL-1β, an NF-κB activator highly expressed in TNBC, increased the promoter activity of SAA1 in human TNBC MDA-MB231 cells. Interestingly, two κB-sites contained in SAA1 promoter were involved, and the proximal region (−96/−87) was more critical than the distal site (−288/−279) in regulating IL-1β-induced SAA1. Among the SAA receptors, TLR1 and TLR2 were highly expressed in TNBC. Cu-CPT22, TLR1/2 antagonist, abrogated IL-1β-induced SAA1 promoter activity. In addition, SAA1 induced IL8/CXCL8 promoter activity, which was partially reduced by Cu-CPT22. Notably, SAA1/2, TLR2 and IL8/CXCL8 were associated with a poor overall survival in mesenchymal-like TNBC. Taken together, IL-1-induced SAA via NF-κB-mediated signaling could potentiate an inflammatory burden, leading to cancer progression and high mortality in TNBC patients.

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“…Recent studies have indicated that GPM6B plays an important role in myelination, neuronal differentiation, and osteoblast differentiation. Some oncology research data have also indicated that GPM6B can be used as a biomarker for gynecological malignancies and breast carcinoma [ 16 , 18 ]. Studies by Fjorback et al [ 14 ] confirmed that the expression of Gpm6B significantly decreased serotonin uptake.…”

Section: Discussionmentioning

confidence: 99%

“…Oncological research on GPM6B has gradually attracted attention in recent years. In breast cancer, GPM6B can be used as a marker of tumor angiogenesis [ 16 ] In a study of the gynecological malignancies, namely, endometrial cancer, uterine cancer, and ovarian cancer, the expression level of Gpm6B was markedly elevated in patient tumor tissues and higher in the peripheral blood of patients than that of healthy controls [ 17 ]. Acting as a protooncogene, GPM6B also upregulates expression in a variety of types of human B lymphocytic leukemia [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

GPM6B Inhibit PCa Proliferation by Blocking Prostate Cancer Cell Serotonin Absorptive Capacity

Huang

et al. 2020

Disease Markers

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Prostate cancer is currently one of the most common fatal tumor types in men. Although multiple treatments can alleviate some cases, advanced prostate cancer, especially CRPC, still has a very poor prognosis. Therefore, early detection and diagnosis of prostate cancer have a very important role in the prognosis of patients. Glycoprotein M6B (GPM6B) is a transmembrane protein that belongs to the proteolipid protein family. GPM6B has been proved and can be used as a biomarker for gynecological malignancies and breast carcinoma. However, there are no studies that explored the functions of GPM6B in PCa. We explored differentially expressed genes in prostate cancer by analyzing TCGA data and found GPM6B downregulated in PCa tissues compared to that in normal prostate tissues. The GPM6B expression in PCa patient’s tumor tissues was significantly related to clinical stage, T classification, lymph node metastasis, and distant metastasis, but not significantly related to age and Gleason score. Also, patients with highGPM6B expression had a better prognosis. The overexpression of GPM6B in prostate cancer cells could inhibit cell proliferation. Serotonin treatment could enhance the proliferation of PCa cell lines; moreover, fluoxetine could reverse this result. In conclusion, we identified GPM6B as a tumor suppressor in PCa. In mechanism, it can regulate the uptaking of serotonin and inhibit the growth of prostate cancer. These results suggested the potential function of GPM6B as a diagnostic marker of PCa and provided clues for the development of new treatment targets for PCa.

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Breast Carcinoma Progression and Tumour Vascular Markers Related to Apoptotic Mechanisms

Cited by 8 publications

References 30 publications

Glycoprotein M6B Interacts with TβRI to Activate TGF-β-Smad2/3 Signaling and Promote Smooth Muscle Cell Differentiation

Glycoprotein M6B Interacts with TβRI to Activate TGF-β-Smad2/3 Signaling and Promote Smooth Muscle Cell Differentiation

Serum amyloid A predisposes inflammatory tumor microenvironment in triple negative breast cancer

GPM6B Inhibit PCa Proliferation by Blocking Prostate Cancer Cell Serotonin Absorptive Capacity

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