scholarly journals Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1882
Author(s):  
Arpita Datta ◽  
Shuo Deng ◽  
Vennila Gopal ◽  
Kenneth Chun-Hong Yap ◽  
Clarissa Esmeralda Halim ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Actin Cytoskeleton ◽  
Cancer Cells ◽  
Intermediate Filaments ◽  
Actin Polymerization ◽  
Cancer Metastasis ◽  
Cellular Transformation ◽  
Actin Binding ◽  
Migration And Invasion ◽  
Mesenchymal Transition

In cancer cells, a vital cellular process during metastasis is the transformation of epithelial cells towards motile mesenchymal cells called the epithelial to mesenchymal transition (EMT). The cytoskeleton is an active network of three intracellular filaments: actin cytoskeleton, microtubules, and intermediate filaments. These filaments play a central role in the structural design and cell behavior and are necessary for EMT. During EMT, epithelial cells undergo a cellular transformation as manifested by cell elongation, migration, and invasion, coordinated by actin cytoskeleton reorganization. The actin cytoskeleton is an extremely dynamic structure, controlled by a balance of assembly and disassembly of actin filaments. Actin-binding proteins regulate the process of actin polymerization and depolymerization. Microtubule reorganization also plays an important role in cell migration and polarization. Intermediate filaments are rearranged, switching to a vimentin-rich network, and this protein is used as a marker for a mesenchymal cell. Hence, targeting EMT by regulating the activities of their key components may be a potential solution to metastasis. This review summarizes the research done on the physiological functions of the cytoskeleton, its role in the EMT process, and its effect on multidrug-resistant (MDR) cancer cells—highlight some future perspectives in cancer therapy by targeting cytoskeleton.

scholarly journals Oxidized Phospholipids in Tumor Microenvironment Stimulate Tumor Metastasis via Regulation of Autophagy

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 558
Author(s):  
Jin Kyung Seok ◽  
Eun-Hee Hong ◽  
Gabsik Yang ◽  
Hye Eun Lee ◽  
Sin-Eun Kim ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Autophagic Flux ◽  
Oxidized Phospholipids ◽  
Mcf7 Cells ◽  
Mesenchymal Transition ◽  
Tumor Tissues

Oxidized phospholipids are well known to play physiological and pathological roles in regulating cellular homeostasis and disease progression. However, their role in cancer metastasis has not been entirely understood. In this study, effects of oxidized phosphatidylcholines such as 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) on epithelial-mesenchymal transition (EMT) and autophagy were determined in cancer cells by immunoblotting and confocal analysis. Metastasis was analyzed by a scratch wound assay and a transwell migration/invasion assay. The concentrations of POVPC and 1-palmitoyl-2-glutaroyl-sn-glycero-phosphocholine (PGPC) in tumor tissues obtained from patients were measured by LC-MS/MS analysis. POVPC induced EMT, resulting in increase of migration and invasion of human hepatocellular carcinoma cells (HepG2) and human breast cancer cells (MCF7). POVPC induced autophagic flux through AMPK-mTOR pathway. Pharmacological inhibition or siRNA knockdown of autophagy decreased migration and invasion of POVPC-treated HepG2 and MCF7 cells. POVPC and PGPC levels were greatly increased at stage II of patient-derived intrahepatic cholangiocarcinoma tissues. PGPC levels were higher in malignant breast tumor tissues than in adjacent nontumor tissues. The results show that oxidized phosphatidylcholines increase metastatic potential of cancer cells by promoting EMT, mediated through autophagy. These suggest the positive regulatory role of oxidized phospholipids accumulated in tumor microenvironment in the regulation of tumorigenesis and metastasis.

scholarly journals Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of AKT/mTOR and Epithelial-to-Mesenchymal Transition

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 638
Author(s):  
Kittipong Sanookpan ◽  
Nongyao Nonpanya ◽  
Boonchoo Sritularak ◽  
Pithi Chanvorachote
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Colony Formation ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. Methods: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. Results: Ovalitenone was used at concentrations of 0–200 μM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. Conclusions: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.

scholarly journals VIP36 preferentially binds to core-fucosylated N-glycans: a molecular docking study

2016 ◽  
Author(s):  
Klaus Fiedler
Keyword(s):  
Epithelial Cells ◽  
Large Scale ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Nonsmall Cell Lung Cancer ◽  
Cellular Transformation ◽  
Molecular Docking Study ◽  
Mesenchymal Transition ◽  
Cargo Receptor ◽  
High Mannose

AbstractAlpha 1-6 fucosyltransferase (Fut8) is known for its properties as an enhancer of nonsmall cell lung cancer metastasis and as a suppressor in hepatocellular carcinoma cells (Hep3B). Promising candidates of affected molecules include E-cadherin. In its absence, during epithelial-mesenchymal transition, the pathway triggers signaling to the nucleus via β-catenin-TCF/LEF. Contrarily, in less metastatic tumors, Fut8 stimulates cell-cell adhesion. Regulated classes of molecules could also include the sorting machinery of polarized epithelial cells, sorted ligands or both, that may be altered in cellular transformation. I have analyzed here the cargo receptor VIP36 (Vesicular-integral membrane protein of 36 kD) for carbohydrate interaction. It has been described as a lectin in the ERGIC (endoplasmic reticulum-Golgi intermediate compartment), Golgi apparatus and plasma membrane. The docking reveals top-interacting carbohydrates of the N-glycan and O-glycan class that encompass N-linked glycans of high mannose and equally complex type which likely function as sorted ligands in epithelial cells. O-glycans score lower and include core 2 residue binding. I show that fucose core modifications by Fut8 stimulate binding of N-linked glycans to VIP36, which is known to be different from binding of galectins 3 and 9. This suggests that Fut8-upregulation may directly alter the affinity of sorted cargo and may enhance the sorting to the apical pathway as exemplified in hepatocytes and traffic to bile. High affinity binding of the ganglioside GM1 carbohydrate headgroup to VIP36 suggests a linkage with protein and glycosphingolipid apical transfer in epithelial cells. Thus, this fundamental approach with large scale docking of 165 carbohydrates including 19 N-glycan high mannose, 17 Nglycan hybrid, 9 N-glycan complex, 17 O-glycan core, 27 Sialoside, 25 Fucoside and 51 other glycan residues suggests, that linked cargo-receptor apical transport may provide a path to epithelial polarization that may be modulated by core fucosylation.

scholarly journals TUBB4B Downregulation Is Critical for Increasing Migration of Metastatic Colon Cancer Cells

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 810 ◽  
Author(s):  
Sobierajska ◽  
Ciszewski ◽  
Wawro ◽  
Wieczorek-Szukała ◽  
Boncela ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Elongation ◽  
Epithelial Mesenchymal Transition ◽  
Cellular Transformation ◽  
Migration And Invasion ◽  
Metastatic Colon Cancer ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Microscopic Studies

Tumor metastasis, the major problem for clinical oncology in colon cancer treatment, is linked with an epithelial-mesenchymal transition (EMT). The observed cellular transformation in this process is manifested by cell elongation, enhanced cell migration and invasion ability, coordinated by cytoskeleton reorganization. In the present study, we examined the role of tubulin-β4 (TUBB4B) downregulation that occurs during EMT in colon cancer cells, in the modulation of the function of microtubules. Based on biochemical and behavioral analysis (transmigration) we posit that the decrease of the TUBB4B level is critical for microtubule-vimentin interaction and contributes to the maintenance of polarity in migrating cells. The microscopic studies revealed that TUBB4B decrease is accompanied by cell elongation and increased number of matured focal adhesion sites, which is a characteristic of the cell metastatic stage. We also demonstrated faster polymerization of microtubules in cells with a lower level of TUBB4B. Simultaneous TUBB3 upregulation, reported during EMT, acts additively in this process. Our studies suggest that the protein level of TUBB4B could be used as a marker for detection of the preinvasive stages of the colon cancer cells. We also concluded that chemotherapy enriched to increase TUBB4B level and/or to stabilize microtubule polymerization might more effectively prevent metastasis in colon cancer development.

scholarly journals Effects of SDF-1/CXCR7 on the Migration, Invasion and Epithelial-Mesenchymal Transition of Gastric Cancer Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Ameng Shi ◽  
Ting Wang ◽  
Miao Jia ◽  
Lei Dong ◽  
Haitao Shi
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Akt Phosphorylation ◽  
Endothelial Growth Factor

We found that SDF-1/CXCR7 axis played an important role in the growth and proliferation of gastric cancer in the previous studies. The objectives of this study were to explore the effects of SDF-1/CXCR7 on the metastatic ability of gastric cancer cells and the possible mechanisms. CXCR7 expression in SGC-7901 gastric cancer cells was stably knocked down via lentiviral vectors. The cell migration and invasion abilities were detected by transwell migration and invasion assays. The expressions of matrix metalloproteinase 2 (MMP-2), MMP-9, vascular endothelial growth factor (VEGF), epithelial-mesenchymal transition (EMT) markers and Akt phosphorylation were detected with real-time PCR and/or western blot. We found that SDF-1 markedly enhanced the migration and invasion abilities of SGC-7901 gastric cancer cells; CXCR7 knockdown inhibited these effects. SDF-1/CXCR7 increased the expressions of MMP-2, MMP-9 and VEGF. SDF-1/CXCR7 also downregulated E-cadherin expression but upregulated N-cadherin, vimentin and Snail expressions, suggesting that SDF-1/CXCR7 could promote the development of EMT in gastric cancer cells. Furthermore, SDF-1/CXCR7 could promote Akt phosphorylation. Our results indicated that SDF-1/CXCR7 enhanced the migration, invasion and EMT of gastric cancer cells and thus CXCR7 supression may be a strategy for inhibiting gastric cancer metastasis.

Mogroside V Inhibits Hyperglycemia-induced Lung Cancer Cells Metastasis through Reversing EMT and Damaging Cytoskeleton

2019 ◽  
Vol 19 (11) ◽  
pp. 885-895
Author(s):  
Jun Chen ◽  
Demin Jiao ◽  
Yu Li ◽  
Chunyan Jiang ◽  
Xiali Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Cellular Proliferation ◽  
Rho Gtpase ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Background: Diabetes Mellitus (DM) accelerates progress of lung cancer. Hyperglycemia, a critical feature of DM, promotes lung cancer metastasis. Mogroside V is a triterpenoid glycoside from Siraitia grosvenorii. Interestingly, mogroside V not only plays an anti-diabetic role, but also has anti-tumor effects. Objective: In this study, we investigated the metastatic efficiency of mogroside V in lung cancer cells cultured in hyperglycemia. Methods: Two lung cancer cell lines-A549 and H1299 were cultured in normoglycemia (5.5mM glucose) and hyperglycemia (25mM glucose). Cellular proliferation was tested by MTT, invasion was examined by transwell assay, migration was measured by wound healing assay, cytoskeleton was stained by Phalloidin-TRITC and the expressions of EMT markers and Rho-GTPase family protein were detected by western blot. Results: Hyperglycemia promoted the invasion and migration of A549 and H1299 cells compared with normoglycemia. Mogroside V inhibited the hyperglycemia-induced invasion and migration. Hyperglycemia promoted epithelial-mesenchymal transition (EMT), while mogroside V could reverse this process through up-regulating E-Cadherin expression and down-regulating N-Cadherin, Vimentin, Snail expressions. Furthermore, mogroside V fractured microfilaments and reduced Rho A, Rac1, Cdc42 and p-PAK1 expressions under hyperglycemic conditions. Conclusion: These results suggest that mogroside V inhibits hyperglycemia-induced lung cancer cells migration and invasion through reversing EMT and damaging cytoskeleton.

scholarly journals OCT4 Suppresses Metastasis in Breast Cancer Cells Through Activation of STAT3 Signaling

2020 ◽  
Author(s):  
Xiangshu Jin ◽  
Yafang Liu ◽  
Huinan Qu ◽  
Da Qi ◽  
Xinqi Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Oct4 Expression ◽  
Stat3 Signaling

Abstract Background: Metastatic breast cancer is the major cause of death in breast cancer patients. Activation of epithelial-mesenchymal transition (EMT) induces migration and invasion of breast cancer cells (BCCs). OCT4 (POU5F1) is a key transcription factor for reprograming and plays an important role in self-renewal. Recent studies recovered OCT4 may correlate with cancer progression. However, it is no sufficient proofs to verify how OCT4 plays in metastasis of breast cancer. In this present study, we show the role of OCT4 in the migration and invasion of BCCs in vitro and metastasis in vivo.Methods: PCR, Western Blot and Immunofluorescence staining were performed to determine to OCT4 expression in BCCs. Wound-healing assay and invasion assay were utilized to analyze the mobility of BCCs. Tumor metastasis was assessed with nude mice by subcutaneously injection. IHC assay was used to evaluate phosphorylated signal transducer and activator of transcription 3 (p-STAT3) expression in breast cancer tissues and normal breast tissues. To study whether OCT4 regulate EMT through STAT3 signal, we used shRNA to knockdown STAT3 gene expression in BCCs.Results: OCT4 changed cell morphology of BCCs, decreased cell adhesion, and inhibited migration, invasion and metastatic ability of BCCs. In the meantime, overexpression of OCT4 activated STAT3 signaling and changed EMT-related protein expressions in BCCs. However, knockdown of STAT3 in BCCs with overexpression of OCT4 could facilitate EMT.Conclusion: Our data demonstrate that OCT4 suppresses EMT in BCCs through activation of STAT3 signaling, which is a key mechanism in impeding BCCs migration and invasion. Collectively, these data suggest that elevating OCT4 expression may be an effective method for reducing the metastatic potential of BCCs, which could also contribute to developing new methods for diagnosis and new molecular target therapies in breast cancer metastasis.

scholarly journals Effects of SDF-1/CXCR7 on the Migration, Invasion and Epithelial-Mesenchymal Transition of Gastric Cancer Cells

2021 ◽  
Author(s):  
Ameng Shi ◽  
Ting Wang ◽  
Miao Jia ◽  
Lei Dong ◽  
Haitao Shi
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Akt Phosphorylation

Abstract We found that SDF-1/CXCR7 axis plays an important role in the growth and proliferation of gastric cancer in previous studies. The objectives of this study were to explore the effects of SDF-1/CXCR7 on the metastatic ability of gastric cancer cells and the possible mechanisms. SGC-7901 gastric cancer cells were cultured in vitro, CXCR7 expression was stably knocked down via lentiviral vectors. The cell migration and invasion abilities were detected by transwell migration and invasion assays. The expression of matrix metalloproteinase 2 (MMP-2), MMP-9, vascular endothelial growth factor (VEGF), epithelial-mesenchymal transition (EMT) markers and Akt phosphorylation were detected with western blot. We found that SDF-1 markedly enhanced the migration and invasion abilities of SGC-7901 gastric cancer cells; CXCR7 knockdown by lentiviral infection inhibited these effects. SDF-1/CXCR7 increased the expression of MMP-2, MMP-9 and VEGF. SDF-1/CXCR7 also downregulated E-cadherin expression but upregulated N-cadherin, vimentin and Snail expression, suggesting that SDF-1/CXCR7 could promote the development of EMT in gastric cancer cells. Furthermore, SDF-1/CXCR7 could promote Akt phosphorylation. Our results indicated that SDF-1/CXCR7 promoted the migration, invasion and EMT of gastric cancer cells and thus CXCR7 inhibition may be a strategy for inhibiting gastric cancer metastasis.

Sign in / Sign up

Export Citation Format

Share Document