Curcumin Inhibits HGF-Induced EMT by Regulating c-MET-Dependent PI3K/Akt/mTOR Signaling Pathways in Meningioma

Meningiomas, which are the most common primary intracranial tumors, have highly aggressive cells in malignant cases. Due to its extensive antitumor effects, curcumin is widely used in experimental and clinical studies. However, the role of curcumin during the epithelial-mesenchymal transition (EMT) in meningioma has not been established. We found that curcumin blocks hepatocyte growth factor- (HGF-) induced proliferation, migration, invasion, and EMT of human malignant meningioma cells by regulating the PI3K/Akt/mTOR signaling pathway. In addition, treatment of human malignant meningioma cells with the tyrosine protein kinase (c-MET) inhibitor (SU11274) or the phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) suppressed HGF-induced migration and EMT. Furthermore, we found that curcumin inhibited tumor growth and HGF-induced EMT in mice subjected to subcutaneous xenotransplantation. These findings indicate that HGF regulates EMT in human malignant meningioma cells through c-MET/PI3K/Akt/mTOR modulation. In conclusion, curcumin inhibits HGF-induced EMT by targeting c-MET and subsequently blocking the PI3K/Akt/mTOR pathway.

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Role of AKT and mTOR signaling pathways in the induction of epithelial-mesenchymal transition (EMT) process

Biochimie ◽

10.1016/j.biochi.2019.08.003 ◽

2019 ◽

Vol 165 ◽

pp. 229-234 ◽

Cited By ~ 22

Author(s):

Mostafa Karimi Roshan ◽

Arash Soltani ◽

Anvar Soleimani ◽

Kolsoum Rezaie Kahkhaie ◽

Amir R. Afshari ◽

...

Keyword(s):

Signaling Pathways ◽

Epithelial Mesenchymal Transition ◽

Mtor Signaling ◽

Mesenchymal Transition

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Macrophages-aPKCɩ-CCL5 Feedback Loop Modulates the Progression and Chemoresistance in Cholangiocarcinoma

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02235-8 ◽

2022 ◽

Vol 41 (1) ◽

Author(s):

Tao Yang ◽

Zhengdong Deng ◽

Lei Xu ◽

Xiangyu Li ◽

Tan Yang ◽

...

Keyword(s):

Cancer Cells ◽

Feedback Loop ◽

Epithelial Mesenchymal Transition ◽

Cationic Liposome ◽

M2 Macrophage ◽

M2 Macrophages ◽

Blood Monocytes ◽

Antitumor Effects ◽

Mesenchymal Transition

Abstract Background Recent data indicated that macrophages may mutually interact with cancer cells to promote tumor progression and chemoresistance, but the interaction in cholangiocarcinoma (CCA) is obscure. Methods 10x Genomics single-cell sequencing technology was used to identified the role of macrophages in CCA. Then, we measured the expression and prognostic role of macrophage markers and aPKCɩ in 70 human CCA tissues. Moreover, we constructed monocyte-derived macrophages (MDMs) generated from peripheral blood monocytes (PBMCs) and polarized them into M1/M2 macrophages. A co-culture assay of the human CCA cell lines (TFK-1, EGI-1) and differentiated PBMCs-macrophages was established, and functional studies in vitro and in vivo was performed to explore the interaction between cancer cells and M2 macrophages. Furthermore, we established the cationic liposome-mediated co-delivery of gemcitabine and aPKCɩ-siRNA and detect the antitumor effects in CCA. Results M2 macrophage showed tumor-promoting properties in CCA. High levels of aPKCɩ expression and M2 macrophage infiltration were associated with metastasis and poor prognosis in CCA patients. Moreover, CCA patients with low M2 macrophages infiltration or low aPKCɩ expression benefited from postoperative gemcitabine-based chemotherapy. Further studies showed that M2 macrophages-derived TGFβ1 induced epithelial-mesenchymal transition (EMT) and gemcitabine resistance in CCA cells through aPKCɩ-mediated NF-κB signaling pathway. Reciprocally, CCL5 was secreted more by CCA cells undergoing aPKCɩ-induced EMT and consequently modulated macrophage recruitment and polarization. Furthermore, the cationic liposome-mediated co-delivery of GEM and aPKCɩ-siRNA significantly inhibited macrophages infiltration and CCA progression. Conclusion our study demonstrates the role of Macrophages-aPKCɩ-CCL5 Feedback Loop in CCA, and proposes a novel therapeutic strategy of aPKCɩ-siRNA and GEM co-delivered by liposomes for CCA.

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Macrophages-aPKCι-CCL5 Feedback Loop Modulates the Progression and Chemoresistance in Cholangiocarcinoma

10.21203/rs.3.rs-921949/v1 ◽

2021 ◽

Author(s):

Tao Yang ◽

Zhengdong Deng ◽

Lei Xu ◽

Xiangyu Li ◽

Tan Yang ◽

...

Keyword(s):

Cancer Cells ◽

Feedback Loop ◽

Epithelial Mesenchymal Transition ◽

Cationic Liposome ◽

M2 Macrophage ◽

M2 Macrophages ◽

Blood Monocytes ◽

Antitumor Effects ◽

Mesenchymal Transition

Abstract Background: Recent data indicated that macrophages may mutually interact with cancer cells to promote tumor progression and chemoresistance, but the interaction in cholangiocarcinoma (CCA) is obscure. Methods: 10x Genomics single-cell sequencing technology was used to identified the role of macrophages in CCA. Then, we measured the expression and prognostic role of macrophage markers and aPKCi in 70 human CCA tissues. Moreover, we constructed monocyte-derived macrophages (MDMs) generated from peripheral blood monocytes (PBMCs) and polarized them into M1/M2 macrophages. A co-culture assay of the human CCA cell lines (TFK-1, EGI-1) and differentiated PBMCs-macrophages was established, and functional studies in vitro and in vivo was performed to explore the interaction between cancer cells and M2 macrophages. Furthermore, we established the cationic liposome-mediated co-delivery of gemcitabine and aPKCi-siRNA and detect the antitumor effects in CCA. Results: M2 macrophage showed tumor-promoting properties in CCA. High levels of aPKCi expression and M2 macrophage infiltration were associated with metastasis and poor prognosis in CCA patients. Moreover, CCA patients with low M2 macrophages infiltration or low aPKCi expression benefited from postoperative gemcitabine-based chemotherapy. Further studies showed that M2 macrophages-derived TGFb1 induced epithelial-mesenchymal transition (EMT) and gemcitabine resistance in CCA cells through aPKCi-mediated NF-kB signaling pathway. Reciprocally, CCL5 was secreted more by CCA cells undergoing aPKCi-induced EMT and consequently modulated macrophage recruitment and polarization. Furthermore, the cationic liposome-mediated co-delivery of GEM and aPKCi-siRNA significantly inhibited macrophages infiltration and CCA progression. Conclusion: our study demonstrates the role of Macrophages-aPKCi-CCL5 Feedback Loop in CCA, and proposes a novel therapeutic strategy of aPKCi-siRNA and GEM co-delivered by liposomes for CCA.

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Magnesium Chloride is an Effective Therapeutic Agent for Prostate Cancer

Functional Foods in Health and Disease ◽

10.31989/ffhd.v8i1.368 ◽

2018 ◽

Vol 8 (1) ◽

pp. 62 ◽

Cited By ~ 2

Author(s):

Julianna Maria Santos ◽

Fazle Hussain

Keyword(s):

Prostate Cancer ◽

Magnesium Chloride ◽

Epithelial Mesenchymal Transition ◽

Chromatin Condensation ◽

Myosin Ii ◽

In Vivo Studies ◽

Migration Speed ◽

Mesenchymal Transition

Background: Reduced levels of magnesium can cause several diseases and increase cancer risk. Motivated by magnesium chloride’s (MgCl2) non-toxicity, physiological importance, and beneficial clinical applications, we studied its action mechanism and possible mechanical, molecular, and physiological effects in prostate cancer with different metastatic potentials.Methods: We examined the effects of MgCl2, after 24 and 48 hours, on apoptosis, cell migration, expression of epithelial mesenchymal transition (EMT) markers, and V-H+-ATPase, myosin II (NMII) and the transcription factor NF Kappa B (NFkB) expressions.Results: MgCl2 induces apoptosis, and significantly decreases migration speed in cancer cells with different metastatic potentials. MgCl2 reduces the expression of V-H+-ATPase and myosin II that facilitates invasion and metastasis, suppresses the expression of vimentin and increases expression of E-cadherin, suggesting a role of MgCl2 in reversing the EMT. MgCl2 also significantly increases the chromatin condensation and decreases NFkB expression.Conclusions: These results suggest a promising preventive and therapeutic role of MgCl2 for prostate cancer. Further studies should explore extending MgCl2 therapy to in vivo studies and other cancer types.Keywords: Magnesium chloride, prostate cancer, migration speed, V-H+-ATPase, and EMT.

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The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor Development

10.21236/ada612714 ◽

2014 ◽

Author(s):

Xin-Hai Pei

Keyword(s):

Mammary Gland ◽

Epithelial Mesenchymal Transition ◽

Tumor Development ◽

Mesenchymal Transition

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Effect of Annexins Translocated in Extracellular Vesicles on Tumorigenesis

Current Molecular Medicine ◽

10.2174/1566524020666200825163512 ◽

2020 ◽

Vol 20 ◽

Author(s):

Qionghui Wu ◽

Haidong Wei ◽

Wenbo Meng ◽

Xiaodong Xie ◽

Zhenchang Zhang ◽

...

Keyword(s):

Tumor Cells ◽

Extracellular Vesicles ◽

Immune Cell ◽

Epithelial Mesenchymal Transition ◽

Main Role ◽

Tumor Cell Adhesion ◽

Mesenchymal Transition ◽

Calcium Dependent ◽

Tumor Neovascularization

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.

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