Mechanism of the Mesenchymal–Epithelial Transition and Its Relationship with Metastatic Tumor Formation

Yao, Dianbo; Dai, Chaoliu; Peng, Songlin

doi:10.1158/1541-7786.mcr-10-0568

Cited by 384 publications

(324 citation statements)

References 135 publications

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“…79 It is therefore likely that increased expression of fibronectin enables tumour cells to adhere to the HSC niche once they have successfully entered the bone microenvironment. 60,68 MET and bone colonisation To enable colonisation of bone, tumour cells undergo a reverse EMT transition known as MET, reactivating their epithelial cell properties and increasing their adhesion and interactions with the bone marrow microenvironment 80,81 (Figure 4). The reexpression of E-cadherin is considered the fundamental hallmark of MET, as it allows tumour cells to interact with the bone marrow and adhere to the HSC niche.…”

Section: Tumour Cell Colonisation and Growth To Bonementioning

confidence: 99%

“…The reexpression of E-cadherin is considered the fundamental hallmark of MET, as it allows tumour cells to interact with the bone marrow and adhere to the HSC niche. 33,80 Once in the bone, tumour cells first form micrometastases that can either proliferate and form overt metastatic lesions or remain dormant for long periods until they reactivate and establish tumours. 82 The mechanisms by which some tumour cells remain dormant whereas others are stimulated to proliferate remain to be established.…”

Section: Tumour Cell Colonisation and Growth To Bonementioning

confidence: 99%

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Molecular alterations that drive breast cancer metastasis to bone

2015

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Epithelial cancers including breast and prostate commonly progress to form incurable bone metastases. For this to occur, cancer cells must adapt their phenotype and behaviour to enable detachment from the primary tumour, invasion into the vasculature, and homing to and subsequent colonisation of bone. It is widely accepted that the metastatic process is driven by the transformation of cancer cells from a sessile epithelial to a motile mesenchymal phenotype through epithelial-mesenchymal transition (EMT). Dissemination of these motile cells into the circulation provides the conduit for cells to metastasise to distant organs. However, accumulating evidence suggests that EMT is not sufficient for metastasis to occur and that specific tissue-homing factors are required for tumour cells to lodge and grow in bone. Once tumour cells are disseminated in the bone environment, they can revert into an epithelial phenotype through the reverse process of mesenchymal-epithelial transition (MET) and form secondary tumours. In this review, we describe the molecular alterations undertaken by breast cancer cells at each stage of the metastatic cascade and discuss how these changes facilitate bone metastasis.

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Section: Tumour Cell Colonisation and Growth To Bonementioning

confidence: 99%

Section: Tumour Cell Colonisation and Growth To Bonementioning

confidence: 99%

Molecular alterations that drive breast cancer metastasis to bone

2015

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“…MET is a feature of both mouse [41] and human [42] somatic cell reprogramming and involves the loss of mesenchymal characteristics such as motility and the acquisition of epithelial characteristics such as cell polarity and expression of the cell adhesion molecule E-CADHERIN, perhaps explaining why E-cadherin can replace Oct4 in the reprogramming process [43] . MET and the opposite transition, epithelial-to-mesenchymal transition (EMT), are key features of embryogenesis [44] , tumour metastasis [45] and both mouse [46] and human [47] ES cell differentiation. Interestingly, the MET that marks the initiation of cellular reprogramming is reversible since removal of the reprogramming factors from mouse "preiPS" cells after induction of reprogramming has been shown to lead to reversion of the cells to a mesenchymal phenotype [36] , thus demonstrating that continued transgene expression is necessary to allow cells to progress to the maturation stage.…”

Section: Initiationmentioning

confidence: 99%

Cell signalling pathways underlying induced pluripotent stem cell reprogramming

Hawkins

Joy

McKay

2014

WJSC

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Induced pluripotent stem (iPS) cells, somatic cells reprogrammed to the pluripotent state by forced expression of defined factors, represent a uniquely valuable resource for research and regenerative medicine. However, this methodology remains inefficient due to incomplete mechanistic understanding of the reprogramming process. In recent years, various groups have endeavoured to interrogate the cell signalling that governs the reprogramming process, including LIF/STAT3, BMP, PI3K, FGF2, Wnt, TGFβ and MAPK pathways, with the aim of increasing our understanding and identifying new mechanisms of improving safety, reproducibility and efficiency. This has led to a unified model of reprogramming that consists of 3 stages: initiation, maturation and stabilisation. Initiation of reprogramming occurs in almost all cells that receive the reprogramming transgenes; most commonly Oct4, Sox2, Klf4 and cMyc , and involves a phenotypic mesenchymal-to-epithelial transition. The initiation stage is also characterised by increased proliferation and a metabolic switch from oxidative phosphorylation to glycolysis. The maturation stage is considered the major bottleneck within the process, resulting in very few "stabilisation competent" cells progressing to the final stabilisation phase. To reach this stage in both mouse and human cells, pre-iPS cells must activate endogenous expression of the core circuitry of pluripotency, comprising Oct4, Sox2, and Nanog , and thus reach a state of transgene independence. By the stabilisation stage, iPS cells generally use the same signalling networks that govern pluripotency in embryonic stem cells. These pathways differ between mouse and human cells although recent work has demonstrated that this is context dependent. As iPS cell generation technologies move forward, tools are being developed to interrogate the process in more detail, thus allowing a greater understanding of this intriguing biological phenomenon.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Pluripotency; Reprogramming; Induced pluripotent stem; Cell signalling; Embryonic stem Core tip: Induced pluripotent stem (iPS) cells present great promise, both to research and to medicine. However, we know very little regarding the mechanisms that occur throughout the iPS cell reprogramming process and thus the process remains inefficient. In this review, we discuss the 3 stages of reprogramming, initiation, maturation and stabilisation, and clarify the signalling pathways underlying each phase. We draw together the current knowledge to propose a model for the interactions between the key pathways in iPS cell reprogramming with the aim of illuminating this complex yet fascinating process.Hawkins K, Joy S, McKay T. Cell signalling pathways underlying induced pluripotent stem cell reprogramming. World J Stem Cells

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“…Inhibiting of this process can help to control of tumor metastasis as a therapeutic strategy in treatment of breast cancer. Several pathways contribute in MET process which can be candidate as therapeutic target (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-124 Overexpression in Associated with Lymph Node Metastasis in Breast Cancer

et al. 2016

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Original PaperBreast cancer is the most frequent cancer and second most common cause of cancer related death in women worldwide (1). Although breast cancer is not a lethal cancer by self, metastasis to distant organs is the main cause of breast cancer mortality and is associated with poor prognosis in breast cancer patients (2-4). Spreading of tumor to auxiliary lymph node is one of the most important factors predicting metastasis of tumor cells (5, 6). Conventional therapeutic strategies includes assessment of local lymph node Breast cancer as a heterogeneous sophisticated disease includes several group with discrete clinical consequences. The disease is the most prevalent malignancy after non-melanoma skin cancers and it is also considered as the second leading cause of death after lung cancer. In fact, breast cancer is account for 23% of all cancer cases and 14% of deaths from cancer. The major cause of breast cancer deaths is actually metastasis of the tumor. As a result, it is prominent to identify the disease mechanism and diagnose molecular tools in order to predict metastasis. The specimens were collected from 30 metastatic and 30 primary tumor tissues of breast cancer patients. After that, RNA extraction was accomplished by means of GeneAll kit and then was stored in -80 degrees. Then, cDNA synthesis was carried out by miscript II RT kit from Qiagenecompany. Finally, sybergreen Real Time PCR of all samples was done for miRNA124, miRNA130a and miRNA 16 as a reference by means of Pre-designed primers of Qiagene Company. The results of molecular expression study showed that the amount of miRNA 124 in metastatic tissues has approximately increased double of primary tumor tissues. It is also revealed that the amount of miRNA has similarly increased by about 1.7 times. According to recent results, it can be possible to regard molecule as a major cause of metastasis process in breast cancer. Keywords

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Mechanism of the Mesenchymal–Epithelial Transition and Its Relationship with Metastatic Tumor Formation

Cited by 384 publications

References 135 publications

Molecular alterations that drive breast cancer metastasis to bone

Molecular alterations that drive breast cancer metastasis to bone

Cell signalling pathways underlying induced pluripotent stem cell reprogramming

MicroRNA-124 Overexpression in Associated with Lymph Node Metastasis in Breast Cancer

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