Epithelial-mesenchymal transition mediates anoikis resistance and enhances invasion in pleural effusion-derived human lung cancer cells

Chunhacha, Preedakorn; Sriuranpong, Virote; Chanvorachote, Pithi

doi:10.3892/ol.2013.1108

Cited by 35 publications

(25 citation statements)

References 15 publications

(43 reference statements)

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“…EMT has been associated with resistance to anoikis, a form of cell death that occurs when cells are detached from their surrounding extracellular matrix (reviewed in refs. 51,52). Anoikis resistance contributes to the ability of cells to survive in altered matrix environments as they travel in circulation to secondary organ sites to form metastases.…”

Section: Discussionmentioning

confidence: 99%

PTK6 Inhibition Suppresses Metastases of Triple-Negative Breast Cancer via SNAIL-Dependent E-Cadherin Regulation

et al. 2016

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Patients with triple-negative breast cancers (TNBC) are at high risk for recurrent or metastatic disease despite standard treatment, underscoring the need for novel therapeutic targets and strategies. Here we report that protein tyrosine kinase 6 (PTK6) is expressed in approximately 70% of TNBCs where it acts to promote survival and metastatic lung colonization. PTK6 downregulation in mesenchymal TNBC cells suppressed migration and three-dimensional culture growth, and enhanced anoikis, resistance to which is considered a prerequisite for metastasis. PTK6 downregulation restored E-cadherin levels via proteasome-dependent degradation of the E-cadherin repressor SNAIL. Beyond being functionally required in TNBC cells, kinase-active PTK6 also suppressed E-cadherin expression, promoted cell migration, and increased levels of mesenchymal markers in nontransformed MCF10A breast epithelial cells, consistent with a role in promoting an epithelial-mesenchymal transition (EMT). SNAIL downregulation and E-cadherin upregulation mediated by PTK6 inhibition induced anoikis, leading to impaired metastatic lung colonization in vivo. Finally, effects of PTK6 downregulation were phenocopied by treatment with a recently developed PTK6 kinase inhibitor, further implicating kinase activity in regulation of EMT and metastases. Our findings illustrate the clinical potential for PTK6 inhibition to improve treatment of patients with high-risk TNBC.Cancer Res; 76(15); 4406-17. Ó2016 AACR.

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Section: Discussionmentioning

confidence: 99%

PTK6 Inhibition Suppresses Metastases of Triple-Negative Breast Cancer via SNAIL-Dependent E-Cadherin Regulation

et al. 2016

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“…A study showed that endothelial cells secreted epidermal growth factor, induced Snail through PI3k‐Akt pathways to form EMT in squamous epithelium cell carcinoma, and obtained stem cell‐like features (aldehyde dehydrogenase and CD44) . Chunhacha et al obtained tumor cells from Thai patients with primary lung cancer with EMT characteristics, showing that tumor suppressor gene p53 effector protein ASPP1 promoted apoptosis protein Bim downregulation and achieved anoikis resistance . These results showed that EMT was one crucial step in tumor metastasis.…”

Section: Discussionmentioning

confidence: 99%

Inhibin B suppresses anoikis resistance and migration through the transforming growth factor‐β signaling pathway in nasopharyngeal carcinoma

et al. 2018

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Inhibin B (INHBB), a heterodimer of a common α‐subunit and a βB‐subunit, is a glycoprotein belonging to the transforming growth factor‐β (TGF‐β) family. In this study, we observed INHBB expression was reduced in nasopharyngeal carcinoma (NPC) tissues compared to non‐tumor nasopharyngeal epithelium tissues, and INHBB was associated with lymph node metastasis, stage of disease, and clinical progress. Positive expression of INHBB in NPC predicted a better prognosis (overall survival, P = 0.038). However, the molecular mechanisms of INHBB have not been addressed in NPC. We induced anoikis‐resistant cells in NPC cell lines under anchorage‐independent conditions, then found epithelial‐mesenchymal transition markers changed, cell apoptosis decreased, cell cycle was modified, and invasion strengthened in anoikis‐resistant NPC cells. These anoikis‐resistant NPC cells showed decreased expression of INHBB compared with adhesion cells. Furthermore, INHBB was found to influence the above‐mentioned changes. In the anoikis‐resistant NPC cells with INHBB overexpression, apoptotic cells increased, S phase cells weakened, vimentin, matrix metallopeptidase‐9, and vascular endothelial growth factor A expression were downregulated, and E‐cadherin expression was upregulated, and vice versa in knockdown of INHBB (INHBB shRNA) anoikis‐resistant NPC cells. Diminished INHBB expression could activate the TGF‐β pathway to phosphorylate Smad2/3 and form complexes in the nucleus, which resulted in the above changes. Thus, our results revealed for the first time that INHBB could suppress anoikis resistance and migration of NPC cells by the TGF‐β signaling pathway, decrease p53 overexpression, and could serve as a potential biomarker for NPC metastasis and prognosis as well as a therapeutic application.

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“…Only 16% of lung cancers are diagnosed when the disease is still localized, while the majority of lung cancers are diagnosed at later stages, which results in a high mortality rate. The initiation and progression of the lung cancer is associated with many factors, including immunity, cytogenetics [35], epithelial-mesenchymal transition [36], and sunlight [37]. Although the immune system with the potential to destroy tumor cells serves as the final natural defense against tumor development, tumor cells can escape from the host immune system by numerous mechanisms which suppress anti-tumor immune function [38].…”

Section: Discussionmentioning

confidence: 99%

Protection Against Lung Cancer Patient Plasma-Induced Lymphocyte Suppression byGanoderma LucidumPolysaccharides

Sun

Lin

et al. 2014

Cell Physiol Biochem

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Background/Aims: This study was conducted to determine the potential of Ganoderma lucidum polysaccharides (Gl-PS) in protection against lung cancer patient plasma-induced suppression of lymphocytes. Lung cancer is a major cause of disease and loss of life in the United States and worldwide. Cancer cells release immunosuppressive mediators, such as PGE2, TGF-β, IL-10, and VEGF, to inhibit the immune response to escape from immune surveillance. Gl-PS has been shown to counteract this immune inhibition in an animal cell culture model, and thus to facilitate tumor control. The present study explored whether or not such an effect could also be demonstrated in human lung cancer patients. Methods: Immunofluorescence, flow cytometry, MTT, immunocytochemistry, and western blot analysis were used to assess lymphocyte activation with PHA. Results: The plasma of lung cancer patients suppressed proliferation, CD69 expression, and perforin and granzyme B production in lymphocytes upon activation by PHA, effects that were partially of fully reversed by Gl-PS. Conclusion: Lung cancer patient plasma-induced suppression of lymphocyte activation by phytohemagglutinin may be antagonized fully or partially by Gl-PS, an observation suggesting the potential of Gl-PS in cancer therapy.

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Epithelial-mesenchymal transition mediates anoikis resistance and enhances invasion in pleural effusion-derived human lung cancer cells

Cited by 35 publications

References 15 publications

PTK6 Inhibition Suppresses Metastases of Triple-Negative Breast Cancer via SNAIL-Dependent E-Cadherin Regulation

PTK6 Inhibition Suppresses Metastases of Triple-Negative Breast Cancer via SNAIL-Dependent E-Cadherin Regulation

Inhibin B suppresses anoikis resistance and migration through the transforming growth factor‐β signaling pathway in nasopharyngeal carcinoma

Protection Against Lung Cancer Patient Plasma-Induced Lymphocyte Suppression byGanoderma LucidumPolysaccharides

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