Linc-ROR induces epithelial-mesenchymal transition and contributes to drug resistance and invasion of breast cancer cells

Tumor Biology ◽  
2016 ◽  
Vol 37 (8) ◽  
pp. 10861-10870 ◽  
Author(s):  
Yao-Min Chen ◽  
Yu Liu ◽  
Hai-Yan Wei ◽  
Ke-Zhen Lv ◽  
Peifen Fu
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals New Advances in the Research of Resistance to Neoadjuvant Chemotherapy in Breast Cancer

2021 ◽  
Vol 22 (17) ◽  
pp. 9644
Author(s):  
Junsha An ◽  
Cheng Peng ◽  
Hailin Tang ◽  
Xiuxiu Liu ◽  
Fu Peng
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Drug Targets ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Treatment Plan ◽  
Mesenchymal Transition ◽  
Chemotherapy Drugs

Breast cancer has an extremely high incidence in women, and its morbidity and mortality rank first among female tumors. With the increasing development of medicine today, the clinical application of neoadjuvant chemotherapy has brought new hope to the treatment of breast cancer. Although the efficacy of neoadjuvant chemotherapy has been confirmed, drug resistance is one of the main reasons for its treatment failure, contributing to the difficulty in the treatment of breast cancer. This article focuses on multiple mechanisms of action and expounds a series of recent research advances that mediate drug resistance in breast cancer cells. Drug metabolizing enzymes can mediate a catalytic reaction to inactivate chemotherapeutic drugs and develop drug resistance. The drug efflux system can reduce the drug concentration in breast cancer cells. The combination of glutathione detoxification system and platinum drugs can cause breast cancer cells to be insensitive to drugs. Changes in drug targets have led to poorer efficacy of HER2 receptor inhibitors. Moreover, autophagy, epithelial–mesenchymal transition, and tumor microenvironment can all contribute to the development of resistance in breast cancer cells. Based on the relevant research on the existing drug resistance mechanism, the current treatment plan for reversing the resistance of breast cancer to neoadjuvant chemotherapy is explored, and the potential drug targets are analyzed, aiming to provide a new idea and strategy to reverse the resistance of neoadjuvant chemotherapy drugs in breast cancer.

scholarly journals A mechanistic model captures the emergence and implications of non-genetic heterogeneity and reversible drug resistance in ER+ breast cancer cells

2021 ◽  
Author(s):  
Sarthak Sahoo ◽  
Ashutosh Mishra ◽  
Harsimran Kaur ◽  
Kishore Hari ◽  
Srinath Muralidharan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Genetic Heterogeneity ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Clonal Selection ◽  
Estrogen Therapy ◽  
Genetic Alterations ◽  
Mesenchymal Transition

Resistance to anti-estrogen therapy is an unsolved clinical challenge in successfully treating ER+ breast cancer patients. Acquisition of mutations can confer heritable resistance to cancer cells, enabling their clonal selection to establish a drug-resistant population. Recent studies have demonstrated that cells can tolerate drug treatment without any genetic alterations too; however, the mechanisms and dynamics of such non-genetic adaptation remain elusive. Here, we investigate coupled dynamics of epithelial-mesenchymal transition (EMT) in breast cancer cells and emergence of reversible drug resistance. Our mechanism-based model for the underlying regulatory network reveals that these two axes can drive one another, thus conferring bidirectional plasticity. This network can also enable non-genetic heterogeneity in a population of cells by allowing for six co-existing phenotypes: epithelial-sensitive, mesenchymal-resistant, hybrid E/M-sensitive, hybrid E/M-resistant, mesenchymal-sensitive and epithelial-resistant, with the first two ones being most dominant. Next, in a population dynamics framework, we exemplify the implications of phenotypic plasticity (both drug-induced and intrinsic stochastic switching) and/or non-genetic heterogeneity in promoting population survival in a mixture of sensitive and resistant cells, even in the absence of any cell-cell cooperation. Finally, we propose the potential therapeutic use of MET (mesenchymal-epithelial transition) inducers besides canonical anti-estrogen therapy to limit the emergence of reversible drug resistance. Our results offer mechanistic insights into empirical observations on EMT and drug resistance and illustrate how such dynamical insights can be exploited for better therapeutic designs.

scholarly journals Emodin-loaded polymer-lipid hybrid nanoparticles enhance the sensitivity of breast cancer to Doxorubicin by inhibiting epithelial mesenchymal transition

2021 ◽  
Author(s):  
Tengteng Zou ◽  
Meng Lan ◽  
Lihong Li ◽  
Tiange Cai ◽  
Yu Cai
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Hybrid Nanoparticles ◽  
Apoptosis Resistance ◽  
Mesenchymal Transition ◽  
Mcf 7

Abstract Background The role of epithelial mesenchymal transition (EMT) involved in breast cancer metastasis and chemoresistance has been increasingly recognized. However, it’s necessary to search for more effective strategies to inhibit EMT thereby increase the sensitivity of breast cancer cells to chemotherapy drugs. Emodin has a potential in overcoming tumor drug resistance and restraining the development of EMT, but the poor internalization into breast cancer cells limited the application. Results MCF-7/ADR cells have more EMT characteristics than MCF-7 cell. EMT in MCF-7/ADR cells promotes the development of drug resistance via apoptosis resistance and facilitating the expression of P-gp. The anti-cancer effect of DOX enhanced by the decreasing of drug resistance protein P-gp and apoptosis related proteins after EMT inhibited in MCF-7/ADR cells. E-PLNs increase the cellular uptake of EMO and restore DOX sensitivity in MCF-7/ADR cells by inhibiting EMT. Conclusion E-PLNs inhibit EMT to enhance the sensitivity of breast cancer to DOX. The combination of E-PLNs and DOX can improve the efficacy of DOX in the treatment of breast cancer, which provides a new method to prevent or delay clinical drug resistance.

scholarly journals A mechanistic model captures the emergence and implications of non-genetic heterogeneity and reversible drug resistance in ER+ breast cancer cells

NAR Cancer ◽  
2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Sarthak Sahoo ◽  
Ashutosh Mishra ◽  
Harsimran Kaur ◽  
Kishore Hari ◽  
Srinath Muralidharan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Genetic Heterogeneity ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mechanistic Model ◽  
Estrogen Therapy ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition

Abstract Resistance to anti-estrogen therapy is an unsolved clinical challenge in successfully treating ER+ breast cancer patients. Recent studies have demonstrated the role of non-genetic (i.e. phenotypic) adaptations in tolerating drug treatments; however, the mechanisms and dynamics of such non-genetic adaptation remain elusive. Here, we investigate coupled dynamics of epithelial–mesenchymal transition (EMT) in breast cancer cells and emergence of reversible drug resistance. Our mechanism-based model for underlying regulatory network reveals that these two axes can drive one another, thus enabling non-genetic heterogeneity in a cell population by allowing for six co-existing phenotypes: epithelial-sensitive, mesenchymal-resistant, hybrid E/M-sensitive, hybrid E/M-resistant, mesenchymal-sensitive and epithelial-resistant, with the first two ones being most dominant. Next, in a population dynamics framework, we exemplify the implications of phenotypic plasticity (both drug-induced and intrinsic stochastic switching) and/or non-genetic heterogeneity in promoting population survival in a mixture of sensitive and resistant cells, even in the absence of any cell–cell cooperation. Finally, we propose the potential therapeutic use of mesenchymal–epithelial transition inducers besides canonical anti-estrogen therapy to limit the emergence of reversible drug resistance. Our results offer mechanistic insights into empirical observations on EMT and drug resistance and illustrate how such dynamical insights can be exploited for better therapeutic designs.

scholarly journals Emodin-loaded polymer-lipid hybrid nanoparticles enhance the sensitivity of breast cancer to doxorubicin by inhibiting epithelial–mesenchymal transition

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tengteng Zou ◽  
Meng Lan ◽  
Fengjie Liu ◽  
Lihong Li ◽  
Tiange Cai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Hybrid Nanoparticles ◽  
Apoptosis Resistance ◽  
Mesenchymal Transition ◽  
Mcf 7

Abstract Background The role of epithelial–mesenchymal transition (EMT) involved in breast cancer metastasis and chemoresistance has been increasingly recognized. However, it is necessary to search for more effective strategies to inhibit EMT thereby increase the sensitivity of breast cancer cells to chemotherapy drugs. Emodin has a potential in overcoming tumor drug resistance and restraining the development of EMT, but the poor internalization into breast cancer cells limited the application. Results MCF-7/ADR cells have more EMT characteristics than MCF-7 cell. EMT in MCF-7/ADR cells promotes the development of drug resistance via apoptosis resistance and facilitating the expression of P-gp. The anti-cancer effect of DOX enhanced by the decreasing of drug resistance protein P-gp and apoptosis-related proteins after EMT inhibited in MCF-7/ADR cells. E-PLNs increase the cellular uptake of EMO and restore DOX sensitivity in MCF-7/ADR cells by inhibiting EMT. Conclusion E-PLNs inhibit EMT to enhance the sensitivity of breast cancer to DOX. The combination of E-PLNs and DOX can improve the efficacy of DOX in the treatment of breast cancer, which provides a new method to prevent or delay clinical drug resistance.

scholarly journals Involvement of the ERK/HIF-1α/EMT Pathway in XCL1-Induced Migration of MDA-MB-231 and SK-BR-3 Breast Cancer Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 89
Author(s):  
Ha Thi Thu Do ◽  
Jungsook Cho
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Chemokine Receptor ◽  
Intracellular Signaling ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mitogen Activated Protein Kinase ◽  
Mesenchymal Transition

Chemokine–receptor interactions play multiple roles in cancer progression. It was reported that the overexpression of X-C motif chemokine receptor 1 (XCR1), a specific receptor for chemokine X-C motif chemokine ligand 1 (XCL1), stimulates the migration of MDA-MB-231 triple-negative breast cancer cells. However, the exact mechanisms of this process remain to be elucidated. Our study found that XCL1 treatment markedly enhanced MDA-MB-231 cell migration. Additionally, XCL1 treatment enhanced epithelial–mesenchymal transition (EMT) of MDA-MB-231 cells via E-cadherin downregulation and upregulation of N-cadherin and vimentin as well as increases in β-catenin nucleus translocation. Furthermore, XCL1 enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Notably, the effects of XCL1 on cell migration and intracellular signaling were negated by knockdown of XCR1 using siRNA, confirming XCR1-mediated actions. Treating MDA-MB-231 cells with U0126, a specific mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, blocked XCL1-induced HIF-1α accumulation and cell migration. The effect of XCL1 on cell migration was also evaluated in ER-/HER2+ SK-BR-3 cells. XCL1 also promoted cell migration, EMT induction, HIF-1α accumulation, and ERK phosphorylation in SK-BR-3 cells. While XCL1 did not exhibit any significant impact on the matrix metalloproteinase (MMP)-2 and -9 expressions in MDA-MB-231 cells, it increased the expression of these enzymes in SK-BR-3 cells. Collectively, our results demonstrate that activation of the ERK/HIF-1α/EMT pathway is involved in the XCL1-induced migration of both MDA-MB-231 and SK-BR-3 breast cancer cells. Based on our findings, the XCL1–XCR1 interaction and its associated signaling molecules may serve as specific targets for the prevention of breast cancer cell migration and metastasis.

scholarly journals A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiraporn Kantapan ◽  
Siwaphon Paksee ◽  
Aphidet Duangya ◽  
Padchanee Sangthong ◽  
Sittiruk Roytrakul ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cell Death ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Cell Lines ◽  
Mesenchymal Transition ◽  
Mammosphere Formation ◽  
Radiation Induced

Abstract Background Radioresistance can pose a significant obstacle to the effective treatment of breast cancers. Epithelial–mesenchymal transition (EMT) is a critical step in the acquisition of stem cell traits and radioresistance. Here, we investigated whether Maprang seed extract (MPSE), a gallotannin-rich extract of seed from Bouea macrophylla Griffith, could inhibit the radiation-induced EMT process and enhance the radiosensitivity of breast cancer cells. Methods Breast cancer cells were pre-treated with MPSE before irradiation (IR), the radiosensitizing activity of MPSE was assessed using the colony formation assay. Radiation-induced EMT and stemness phenotype were identified using breast cancer stem cells (CSCs) marker (CD24−/low/CD44+) and mammosphere formation assay. Cell motility was determined via the wound healing assay and transwell migration. Radiation-induced cell death was assessed via the apoptosis assay and SA-β-galactosidase staining for cellular senescence. CSCs- and EMT-related genes were confirmed by real-time PCR (qPCR) and Western blotting. Results Pre-treated with MPSE before irradiation could reduce the clonogenic activity and enhance radiosensitivity of breast cancer cell lines with sensitization enhancement ratios (SERs) of 2.33 and 1.35 for MCF7 and MDA-MB231cells, respectively. Pretreatment of breast cancer cells followed by IR resulted in an increased level of DNA damage maker (γ-H2A histone family member) and enhanced radiation-induced cell death. Irradiation induced EMT process, which displayed a significant EMT phenotype with a down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker vimentin in comparison with untreated breast cancer cells. Notably, we observed that pretreatment with MPSE attenuated the radiation-induced EMT process and decrease some stemness-like properties characterized by mammosphere formation and the CSC marker. Furthermore, pretreatment with MPSE attenuated the radiation-induced activation of the pro-survival pathway by decrease the expression of phosphorylation of ERK and AKT and sensitized breast cancer cells to radiation. Conclusion MPSE enhanced the radiosensitivity of breast cancer cells by enhancing IR-induced DNA damage and cell death, and attenuating the IR-induced EMT process and stemness phenotype via targeting survival pathways PI3K/AKT and MAPK in irradiated breast cancer cells. Our findings describe a novel strategy for increasing the efficacy of radiotherapy for breast cancer patients using a safer and low-cost natural product, MPSE.

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