Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

Zhang, Jinfeng; Zhang, Jian; Xu, Shouping; Zhang, Xianyu; Wang, Peiyuan; Wu, Hao; Xia, Bo; Zhang, Guangwen; Lei, Bo; Wan, Lin; Zhang, Dekai; Pang, Da

doi:10.1159/000487162

Cited by 43 publications

(37 citation statements)

References 48 publications

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“…Indeed, both the mRNA expression and protein levels of this molecule have been shown to be significantly decreased in colorectal cancer compared with paired adjacent normal tissue (218). In breast cancer, the downregulated expression of this protein is due to its promoter methylation, induced by hypoxia, leading to cell invasiveness, poor prognosis and chemoresistance (219). In another independent study, Shin et al found that the loss of Tpm2.1 increased the efficiency of migration of breast cancer cells out of the spheroids on different coated extracellular matrices (220).…”

Section: Cytoskeletonmentioning

confidence: 99%

Biomarkers of tumor invasiveness in proteomics (Review)

et al. 2020

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Over the past two decades, quantitative proteomics has emerged as an important tool for deciphering the complex molecular events involved in cancers. The number of references involving studies on the cancer metastatic process has doubled since 2010, while the last 5 years have seen the development of novel technologies combining deep proteome coverage capabilities with quantitative consistency and accuracy. To highlight key findings within this huge amount of information, the present review identified a list of tumor invasive biomarkers based on both the literature and data collected on a biocollection of experimental cell lines, tumor models of increasing invasiveness and tumor samples from patients with colorectal or breast cancer. Crossing these different data sources led to 76 proteins of interest out of 1,245 mentioned in the literature. Information on these proteins can potentially be translated into clinical prospects, since they represent potential targets for the development and evaluation of innovative therapies, alone or in combination. Herein, a systematical review of the biology of each of these proteins, including their specific subcellular/extracellular or multiple localizations is presented. Finally, as an important advantage of quantitative proteomics is the ability to provide data on all these molecules simultaneously in cell pellets, body fluids or paraffin-embedded sections of tumors/invaded tissues, the significance of some of their interconnections is discussed.

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Section: Cytoskeletonmentioning

confidence: 99%

Biomarkers of tumor invasiveness in proteomics (Review)

et al. 2020

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“…The cores of tumors are often chronically hypoxic, which is closely associated with a negative prognosis and a metastatic phenotype which is more resistant to cancer therapy [15, 16]. By targeting the hypoxic core of primary and metastatic sites, PNA may act to enhance blood flow and improve the therapeutic effects of standard chemotherapy, radiotherapy, and/or immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Use of Antimetastatic SOD3-Mimetic Albumin as a Primer in Triple Negative Breast Cancer

Messerli

Schaefer

Zhuang

et al. 2019

Journal of Oncology

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Of the deaths attributed to cancer, 90% are due to metastasis. Treatments that prevent or cure metastasis remain elusive. Low expression of extracellular superoxide dismutase (EcSOD or SOD3) has been associated with poor outcomes and increased metastatic potential in multiple types of cancer. Here, we characterize the antimetastatic therapeutic mechanisms of a macromolecular extracellular SOD3-mimetic polynitroxyl albumin (PNA, also known as VACNO). PNA is macromolecular human serum albumin conjugated with multiple nitroxide groups and acts as an SOD-mimetic. Here we show that PNA works as a SOD3-mimetic in a highly metastatic 4T1 mouse model of triple negative breast cancer (TNBC). In vitro, PNA dose dependently inhibited 4T1 proliferation, colony formation, and reactive oxygen species (ROS) formation. In vivo, PNA enhanced reperfusion time in the hypoxic cores of 4T1 tumors as measured by ultrasound imaging. Furthermore, PNA enhanced ultrasound signal intensity within the cores of the 4T1 tumors, indicating PNA can increase blood flow and blood volume within the hypoxic cores of tumors. Lung metastasis from 4T1 flank tumor was inhibited by PNA in the presence or absence of doxorubicin, a chemotherapy agent that produces superoxide and promotes metastasis. In a separate study, PNA increased the survival of mice with 4T1 flank tumors when used in conjunction with three standard chemotherapy drugs (paclitaxel, doxorubicin, and cyclophosphamide), as compared to treatment with chemotherapy alone. In this study, PNA-increased survival was also correlated with reduction of lung metastasis. These results support the hypothesis that PNA works through the inhibition of extracellular superoxide/ROS production leading to the conversion of 4T1 cells from a metastatic tumorigenic state to a cytostatic state. These findings support future clinical trials of PNA as an antimetastatic SOD3-mimetic drug to increase overall survival in TNBC patients.

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“…Following the analysis of the public and private datasets, the expression of TPM2 in the atherosclerotic tissues was observed to be lower than in normal tissues. TPM2 is a subtype of tropomyosin [28]. Tropomyosin (TPM), a thin filament-associated protein, and has been hypothesized to serve a crucial role in the regulation of muscle contraction [29].…”

Section: Discussionmentioning

confidence: 99%

TPM2 as a potential predictive biomarker for atherosclerosis

Meng

Shan

Qiu

et al. 2019

Aging

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Cardiac-cerebral vascular disease (CCVD), is primarily induced by atherosclerosis, and is a leading cause of mortality. Numerous studies have investigated and attempted to clarify the molecular mechanisms of atherosclerosis; however, its pathogenesis has yet to be completely elucidated. Two expression profiling datasets, GSE43292 and GSE57691, were obtained from the Gene Expression Omnibus (GEO) database. The present study then identified the differentially expressed genes (DEGs), and functional annotation of the DEGs was performed. Finally, an atherosclerosis animal model and neural network prediction model was constructed to verify the relationship between hub gene and atherosclerosis. The results identified a total of 234 DEGs between the normal and atherosclerosis samples. The DEGs were mainly enriched in actin filament, actin binding, smooth muscle cells, and cytokine-cytokine receptor interactions. A total of 13 genes were identified as hub genes. Following verification of animal model, the common DEG, Tropomyosin 2 (TPM2), was found, which were displayed at lower levels in the atherosclerosis models and samples. In summary, DEGs identified in the present study may assist clinicians in understanding the pathogenesis governing the occurrence and development of atherosclerosis, and TPM2 exhibits potential as a promising diagnostic and therapeutic biomarker for atherosclerosis.

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Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

Cited by 43 publications

References 48 publications

Biomarkers of tumor invasiveness in proteomics (Review)

Biomarkers of tumor invasiveness in proteomics (Review)

Use of Antimetastatic SOD3-Mimetic Albumin as a Primer in Triple Negative Breast Cancer

TPM2 as a potential predictive biomarker for atherosclerosis

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