<scp>EMT</scp> and <scp>MET</scp>: necessary or permissive for metastasis?

Jolly, Mohit Kumar; Ware, Kathryn E.; Gilja, Shivee; Somarelli, Jason A.; Levine, Herbert

doi:10.1002/1878-0261.12083

Cited by 318 publications

(229 citation statements)

References 146 publications

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“…The potential relevance of EMT to metastasis is largely based on in vitro studies using transformed epithelial cells and experimental manipulations. [59] Tumors consist of genetically unstable cells and infiltrating cells could contribute to shifts in linage markers. The gain or loss of markers seems insufficient to assume a whole-scale gene expression reprogramming of a cell type.…”

Section: Emtmentioning

confidence: 99%

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Circulating Tumor Cells in the Parallel Invasion Model Supporting Early Metastasis

Hamilton¹,

Rath²

2018

Oncomedicine

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Circulating tumor cells (CTCs) seem to comprise metastasis-initiating cells and their count and phenotype represent an indicator of prognosis and response to therapy in cancer patients. In the classical model of tumor dissemination, specialized cells at the invasive front undergo epithelial-mesenchymal transition (EMT) and enter peripheral tumor-coalescing blood vessels to establish metastatic lesions by extravasation of CTCs. Thus, dissemination of cancer cells occurs after prolonged tumor development and following access to neighboring blood vessels via transit through stromal tissue. However, clinical and new experimental data indicate early tumor dissemination immediately after an angiogenic switch has occurred and an intravasation of tumor cells in the tumor core region. Accordingly, CTCs may have direct access through fenestrated and irregular intratumoral vessels and, therefore, the metastasis-initiating cells become active a long time before lesions are detected clinically. This model of cancer cell intravasation is better compatible with the release of CTC clusters and apoptotic CTCs and, furthermore, spares the requirement for an elusive and complicated EMT/MET program. Similarly, the intravasation of large number of CTCs observed in metastatic disease may be alleviated by an intratumoral process instead of a stromal crossing. This early metastasis model changes the possible pathways targeted for the prevention and inhibition of metastasis and the significance of CTCs which are detected and analyzed late after the initial phase of tumor dissemination.

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Section: Emtmentioning

confidence: 99%

“…[59] The EMT is primarily considered a phenomenon of the in vitro environment. [60] It is not clear whether alternative regulatory programs can also enable EMT-like capability.…”

Section: Emtmentioning

confidence: 99%

Circulating Tumor Cells in the Parallel Invasion Model Supporting Early Metastasis

Hamilton¹,

Rath²

2018

Oncomedicine

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“…However, several studies have shown that disseminated cancer cells in metastatic sites are more like epithelial cells compared to cancer cells in primary tumors in a number of different types of carcinomas, including prostate cancer, breast cancer, colorectal cancer, pulmonary cancer and hepatic carcinomas. To explain this contradiction, a MET process was assumed to be involved in the formation process of metastatic tumors [4,5]. Epigenetic regulation of metastasis suppressor genes promises to be a potentially important mechanism by which dietary components can moluate cancer metastasis since many phytochemicals are known to modulate gene expression [4,6,7].…”

Section: Cancer Metastasismentioning

confidence: 99%

“…It is a very important cancer-preventing mechanism to epithelial tissues because anoikis mechanism facilitates the elimination of unattached epithelial cells, which have been shed from the epithelium in the high-rate epithelium turnover process, to prevent these cells from attaching to inappropriate sites. Inappropriate attachment may lead to extensive neoplastic growth and cause cancers [5,8,9].…”

Section: Emt and Anoikismentioning

confidence: 99%

“…Previous studies have indicated that cell detachment causes cell death, anoikis, in normal epithelial cells but not in those cancerous epithelial cells which have been through EMT because in the EMT process, cancer cells will gain the resistance to anoikis for surviving as they become more malignant [5,9]. Two studies have strongly supported that E-cadherin-mediated cell interaction between normal epithelial cells sensitizes detached epithelial cells to anoikis [10].…”

Section: Emt and Anoikismentioning

confidence: 99%

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Untitled

2017

JAPLR

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Cancer development, a dynamic and long-term process, involves many complex factors with stepwise progression ultimately leading to uncontrolled spreading and growth of cancerous cells throughout the body called metastasis. The three critical steps in this process for several types of human cancer formation are initiation, promotion and progression. Invasion and metastasis are fundamental properties of malignant cancer cells. In advanced tumors, EMT (epithelialmesenchymal transition) and mesenchymal-epithilial transition (MET) is commonly associated with acquisition of metastatic potential. Chemoprevention, a relatively new and promising strategy to prevent cancer, is defined as the use of natural dietary compounds and/or synthetic substances to block, inhibit, reverse, or retard the process of tumorigenesis. The chemopreventive effects elicited by these natural dietary compounds are believed to be the properties include antioxidative, anti-inflammatory activity, induction of phase 2 enzymes, apoptosis, and cell cycle arrest. In this review, we will discuss the phytochemicals on the potential molecular targets and signalling pathways that mediate tumour metastasis.

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Single‐cell protein profiling defines cell populations associated with triple‐negative breast cancer aggressiveness

et al. 2023

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Triple‐negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic, extensive intratumoral heterogeneity that promotes disease progression and influences drug response. Single‐cell techniques in combination with next‐generation computation provide an unprecedented opportunity to identify molecular events with therapeutic potential. Here, we describe the generation of a comprehensive mass cytometry panel for multiparametric detection of 23 phenotypic markers and 13 signaling molecules. This single‐cell proteomic approach allowed us to explore the landscape of TNBC heterogeneity, with particular emphasis on the tumor microenvironment. We prospectively profiled freshly resected tumors from 26 TNBC patients. These tumors contained phenotypically distinct subpopulations of cancer and stromal cells that were associated with the patient's clinical status at the time of surgery. We further classified the epithelial‐mesenchymal plasticity of tumor cells, and molecularly defined phenotypically diverse populations of tumor‐associated stroma. Furthermore, in a retrospective tissue‐microarray TNBC cohort, we showed that the level of CD97 at the time of surgery has prognostic potential.

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EMT and MET: necessary or permissive for metastasis?

Cited by 318 publications

References 146 publications

Circulating Tumor Cells in the Parallel Invasion Model Supporting Early Metastasis

Circulating Tumor Cells in the Parallel Invasion Model Supporting Early Metastasis

Untitled

Single‐cell protein profiling defines cell populations associated with triple‐negative breast cancer aggressiveness

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