The role of EMT and MET in cancer dissemination

Banyard, Jacqueline; Bielenberg, Diane R.

doi:10.3109/03008207.2015.1060970

Cited by 216 publications

(201 citation statements)

References 102 publications

(121 reference statements)

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“…Development and survival of multicellular organisms rely on the dynamic regulation of MET and EMT [29]. Disruption of this equilibrium and a shift to a more mesenchymal phenotype can mediate tumor cell intravasation of surrounding blood vessels and emigration to a new organ [42]. …”

Section: Discussionmentioning

confidence: 99%

Nectin-1 Expression in Colorectal Cancer: Is There a Group of Patients with High Risk for Early Disease Recurrence?

et al. 2019

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Background: Despite improvements in therapy of colorectal cancer, some patients will present occurrence of recurrence either locally or distantly. Tumor metastasis constitutes the major cause of cancer-associated morbidity and mortality. Nectin-1 belongs to the family of immunoglobulin-like cell adhesion molecules that contribute to the formation of cell-cell adhesions and regulate a series of cellular activities including cell polarization, differentiation, movement, proliferation, and survival. Expression of Nectin-1 in malignant tumors has been associated with aggressive tumor phenotypes. Objectives: The aim of the present study was to assess Nectin-1 expression patterns in colorectal cancer and to investigate its clinical significance. Methods: Nectin-1 expression was assessed via immunohistochemistry in surgical specimens of a cohort comprised of 111 patients with primary resectable colorectal cancer. Results were correlated with clinicopathological characteristics and survival data. Progression-free survival was defined as the primary outcome of the present study. Results: Nectin-1 was strongly expressed in the cytoplasm of colorectal cancer cells. High Nectin-1 expression was associated with advanced stage of disease (p = 0.012) and lymph node metastasis (p = 0.007). Progression-free survival of patients exhibiting high expression of Nectin-1 in the first 36 months after surgery was significantly worse compared to patients with low expression of Nectin-1 (55.7%, 95% CI = 47–70, vs. 82.1%, 95% CI = 69–93, p = 0.014) and independent of other clinicopathological characteristics (HR = 0.389, 95% CI = 0.156–0.972, p = 0.043). Conclusion: Nectin-1 expression in colorectal cancer is associated with a significantly worse 3-year progression-free survival identifying therefore a group of patients with high risk for early disease recurrence.

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Section: Discussionmentioning

confidence: 99%

Nectin-1 Expression in Colorectal Cancer: Is There a Group of Patients with High Risk for Early Disease Recurrence?

et al. 2019

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“…From the earliest phases of tumour development, neoplastic cells, including CTCs, are actively shed into the bloodstream through the epithelial-to-mesenchymal transition (EMT) [21, 22]. The expression of EMT markers is associated with enhanced CTC invasion and migration as well as enhanced resistance to apoptosis and necrosis [23].…”

Section: Circulating Tumour Cellsmentioning

confidence: 99%

Circulating Tumour Cells in Predictive Molecular Pathology: Focus on Drug-Sensitive Assays and 3D Culture

et al. 2019

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Molecular cytopathology is a rapidly evolving field of cytopathology that provides biological information about the response to personalised therapy and about the prognosis of neoplasms diagnosed on cytological samples. Biomarkers such as circulating tumour cells and circulating tumour DNA are increasingly being evaluated in blood and in other body fluids. Such liquid biopsies are non-invasive, repeatable, and feasible also in patients with severe comorbidities. However, liquid biopsy may be challenging due to a low concentration of biomarkers. In such cases, biomarkers can be detected with highly sensitive molecular techniques, which in turn should be validated and integrated in a complex algorithm that includes tissue-based molecular assessments. The aim of this review is to provide the cytopathologist with practical information that is relevant to daily practice, particularly regarding the emerging role of circulating tumour cells in the field of predictive molecular pathology.

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“…Through this exosomal regulation, gastric cancer cells may become more prone to invade the serosa and exfoliate into the cavity with increased proliferative and migratory abilities. Epithelial cells express high levels of epithelial (E)-cadherin, while mesenchymal cells express neural (N)-cadherin, fibronectin and vimentin (14). Dysfunction of E-cadherin has been implicated in gastric cancer progression and may predominantly contribute to invasion of the gastric wall and migration of cancer cells into the free abdominal space (3).…”

Section: Exosomes In Peritoneal Dissemination Of Gastric Cancermentioning

confidence: 99%

“…Furthermore, matrix metalloproteinases (MMPs), as the effectors of EMT, have also been identified in exosomes (14). MMP-7 expression has been significantly associated with serosal infiltration and TNM stage in gastric cancer (16).…”

Section: Exosomes In Peritoneal Dissemination Of Gastric Cancermentioning

confidence: 99%

Exosome‑mediated peritoneal dissemination in gastric cancer and its clinical applications (Review)

Chen

Jin

et al. 2018

biom rep

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Abstract. The prognosis of patients with peritoneal dissemination from gastric cancer is poor, and the underlying molecular mechanism remains unclear. Exosomes, as macromolecular phospholipid bilayer vesicles comprising of proteins, nucleic acids and lipids, serve as mediators of cell-cell communication. Gastric cancer tumor-derived exosomes may be involved in the pathological process of peritoneal dissemination by mediating crosstalk between cancer cells and mesothelial cells, to result in the induction of enhanced tumor growth, migratory, adhesive and invasive abilities, peritoneal fibrosis and apoptosis, mesothelial-to-mesenchymal transition, angiogenesis and chemoresistance. The present review focuses on previous studies addressing the exosome-dependent molecular transfer in peritoneal dissemination in gastric cancer and the potential clinical applications. Contents1. Introduction 2. Exosomes in peritoneal dissemination of gastric cancer 3. Early detection by exosomal miRNAs 4. Chemoresistance and exosome-based treatment of peritoneal dissemination cases of gastric cancer IntroductionPeritoneal dissemination is detected in 14% of patients with gastric cancer at the time of initial diagnosis, for whom the median survival time is 4 months (1). Gastric cancer patients with peritoneal dissemination cannot undergo radical surgery, and the chemotherapeutic effect is limited due to inadequate distribution of intravenous chemotherapy drugs, blocked by the peritoneal barrier, and tumor chemoresistance (2). The 5-year survival rate of gastric cancer patients with peritoneal dissemination is only 2% (3). Peritoneal dissemination is among the most common patterns of recurrence in gastric cancer patients (4). However, it remains unclear how peritoneal dissemination exactly occurs, and there is a need to reveal the underlying molecular mechanism, as well as to develop more effective treatment strategies. Exosomes are macromolecular, phospholipid bilayer vesicles comprised of proteins, nucleic acids and lipids (5). At 40-120 nm in diameter, exosomes are smaller than other vesicles including microvesicles (100 nm-1 µm) and apoptotic bodies (50 nm-2 µm) (6). Exosomes exist in all body fluids and are generated by secretion and budding from various types of cells, including tumor cells (7). They contain key biological molecules including proteins, RNAs and lipids, which are considered to mediate intercellular communication (6). In particular, exosomes deliver proteins and RNAs associated with different pathologies, including neurodegenerative diseases, HIV infection, heart disease and tumor progression, from host cells to recipient cells (8). Tumor-derived exosomes (TEX) may have the capacity to remodel the tumor microenvironment to make it favorable for metastatic niches (7) and, furthermore, may alter the extracellular matrix and attract more cancer cells to the niches (9). Notably, increasing studies indicate that exosomes are involved in the peritoneal dissemination of gastric cancer. The present review focuses on how exos...

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The role of EMT and MET in cancer dissemination

Cited by 216 publications

References 102 publications

Nectin-1 Expression in Colorectal Cancer: Is There a Group of Patients with High Risk for Early Disease Recurrence?

Nectin-1 Expression in Colorectal Cancer: Is There a Group of Patients with High Risk for Early Disease Recurrence?

Circulating Tumour Cells in Predictive Molecular Pathology: Focus on Drug-Sensitive Assays and 3D Culture

Exosome‑mediated peritoneal dissemination in gastric cancer and its clinical applications (Review)

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