scholarly journals Non-muscle myosin IIB is critical for nuclear translocation during 3D invasion

2015 ◽  
Vol 210 (4) ◽  
pp. 583-594 ◽  
Author(s):  
Dustin G. Thomas ◽  
Aishwarya Yenepalli ◽  
Celine Marie Denais ◽  
Andrew Rape ◽  
Jordan R. Beach ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Metastasis ◽  
Nuclear Translocation ◽  
Three Dimensional ◽  
Traction Force ◽  
Embryonic Cell ◽  
Migration And Invasion ◽  
Force Microscopy ◽  
Gland Carcinoma ◽  
Muscle Myosin

Non-muscle myosin II (NMII) is reported to play multiple roles during cell migration and invasion. However, the exact biophysical roles of different NMII isoforms during these processes remain poorly understood. We analyzed the contributions of NMIIA and NMIIB in three-dimensional (3D) migration and in generating the forces required for efficient invasion by mammary gland carcinoma cells. Using traction force microscopy and microfluidic invasion devices, we demonstrated that NMIIA is critical for generating force during active protrusion, and NMIIB plays a major role in applying force on the nucleus to facilitate nuclear translocation through tight spaces. We further demonstrate that the nuclear membrane protein nesprin-2 is a possible linker coupling NMIIB-based force generation to nuclear translocation. Together, these data reveal a central biophysical role for NMIIB in nuclear translocation during 3D invasive migration, a result with relevance not only to cancer metastasis but for 3D migration in other settings such as embryonic cell migration and wound healing.

scholarly journals Erianthridin suppresses non-small-cell lung cancer cell metastasis through inhibition of Akt/mTOR/p70S6K signaling pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sutthaorn Pothongsrisit ◽  
Kuntarat Arunrungvichian ◽  
Yoshihiro Hayakawa ◽  
Boonchoo Sritularak ◽  
Supachoke Mangmool ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Protein Kinase ◽  
Small Cell Lung Cancer ◽  
Cancer Metastasis ◽  
Small Cell ◽  
Migration And Invasion ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
Cell Metastasis

AbstractCancer metastasis is a major cause of the high mortality rate in lung cancer patients. The cytoskeletal rearrangement and degradation of extracellular matrix are required to facilitate cell migration and invasion and the suppression of these behaviors is an intriguing approach to minimize cancer metastasis. Even though Erianthridin (ETD), a phenolic compound isolated from the Thai orchid Dendrobium formosum exhibits various biological activities, the molecular mechanism of ETD for anti-cancer activity is unclear. In this study, we found that noncytotoxic concentrations of ETD (≤ 50 μM) were able to significantly inhibit cell migration and invasion via disruption of actin stress fibers and lamellipodia formation. The expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 was markedly downregulated in a dose-dependent manner after ETD treatment. Mechanistic studies revealed that protein kinase B (Akt) and its downstream effectors mammalian target of rapamycin (mTOR) and p70 S6 kinase (p70S6K) were strongly attenuated. An in silico study further demonstrated that ETD binds to the protein kinase domain of Akt with both hydrogen bonding and van der Waals interactions. In addition, an in vivo tail vein injection metastasis study demonstrated a significant effect of ETD on the suppression of lung cancer cell metastasis. This study provides preclinical information regarding ETD, which exhibits promising antimetastatic activity against non-small-cell lung cancer through Akt/mTOR/p70S6K-induced actin reorganization and MMPs expression.

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 Different Cell Migration Modes: Insights from Traction Force Microscopy and Modeling

2021 ◽  
Vol 120 (3) ◽  
pp. 113a
Author(s):  
Wouter-Jan Rappel ◽  
Elisabeth Ghabache ◽  
Yuansheng Cao ◽  
Yuchuan Miao ◽  
Alexander Groisman ◽  
...  
Keyword(s):  
Cell Migration ◽  
Traction Force ◽  
Traction Force Microscopy ◽  
Force Microscopy

scholarly journals Epifluorescence-based three-dimensional traction force microscopy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lauren Hazlett ◽  
Alexander K. Landauer ◽  
Mohak Patel ◽  
Hadley A. Witt ◽  
Jin Yang ◽  
...  
Keyword(s):  
Spatial Frequency ◽  
Open Source ◽  
Single Particle ◽  
Three Dimensional ◽  
Traction Force ◽  
High Spatial Frequency ◽  
Epifluorescence Microscopy ◽  
Traction Force Microscopy ◽  
Force Microscopy ◽  
Out Of Plane

Abstract We introduce a novel method to compute three-dimensional (3D) displacements and both in-plane and out-of-plane tractions on nominally planar transparent materials using standard epifluorescence microscopy. Despite the importance of out-of-plane components to fully understanding cell behavior, epifluorescence images are generally not used for 3D traction force microscopy (TFM) experiments due to limitations in spatial resolution and measuring out-of-plane motion. To extend an epifluorescence-based technique to 3D, we employ a topology-based single particle tracking algorithm to reconstruct high spatial-frequency 3D motion fields from densely seeded single-particle layer images. Using an open-source finite element (FE) based solver, we then compute the 3D full-field stress and strain and surface traction fields. We demonstrate this technique by measuring tractions generated by both single human neutrophils and multicellular monolayers of Madin–Darby canine kidney cells, highlighting its acuity in reconstructing both individual and collective cellular tractions. In summary, this represents a new, easily accessible method for calculating fully three-dimensional displacement and 3D surface tractions at high spatial frequency from epifluorescence images. We released and support the complete technique as a free and open-source code package.

scholarly journals Collective forces of tumor spheroids in three-dimensional biopolymer networks

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Christoph Mark ◽  
Thomas J Grundy ◽  
Pamela L Strissel ◽  
David Böhringer ◽  
Nadine Grummel ◽  
...  
Keyword(s):  
Single Cells ◽  
Three Dimensional ◽  
Traction Force ◽  
Tumor Spheroids ◽  
Scale Invariant ◽  
Tissue Samples ◽  
Force Microscopy ◽  
Surrounding Matrix ◽  
Highly Nonlinear ◽  
Contractile Forces

We describe a method for quantifying the contractile forces that tumor spheroids collectively exert on highly nonlinear three-dimensional collagen networks. While three-dimensional traction force microscopy for single cells in a nonlinear matrix is computationally complex due to the variable cell shape, here we exploit the spherical symmetry of tumor spheroids to derive a scale-invariant relationship between spheroid contractility and the surrounding matrix deformations. This relationship allows us to directly translate the magnitude of matrix deformations to the total contractility of arbitrarily sized spheroids. We show that our method is accurate up to strains of 50% and remains valid even for irregularly shaped tissue samples when considering only the deformations in the far field. Finally, we demonstrate that collective forces of tumor spheroids reflect the contractility of individual cells for up to 1 hr after seeding, while collective forces on longer timescales are guided by mechanical feedback from the extracellular matrix.

scholarly journals PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Qingmin Sun ◽  
Mengyun Yuan ◽  
Hongxing Wang ◽  
Xingxing Zhang ◽  
Ruijuan Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Nuclear Translocation ◽  
Aerobic Glycolysis ◽  
Metabolic Reprogramming ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition

Gastric cancer is the third leading cause of cancer death worldwide. Traditional Chinese medicine (TCM) is increasingly extensively applied as a complementary therapy for gastric cancer (GC) in China, which shows unique advantages in preventing gastric cancer metastasis. Previous study indicates modified Jian-pi-yang-zheng (mJPYZ) decoction inhibit the progression of gastric cancer by regulating tumor-associated macrophages (TAM). However, it is unclear whether mJPYZ can affect metabolic reprogramming of gastric cancer cells. Here, we showed that mJPYZ effectively attenuated GC cells proliferation, migration and invasion. Meantime, mJPYZ reduced the aerobic glycolysis level of GC cells in vivo and in vitro by regulating the expression and nuclear translocation of PKM2. Overexpression of PKM2 that could reverse the inhibitory effect of mJPYZ, migration and epithelial to mesenchymal transition (EMT). Our results showed PKM2/HIF-1α signaling was the key metabolic regulator of mJPYZ in GC cells. In summary, our present study suggested that abnormal PKM2 is required for maintaining the malignant phenotype of GC cells. The TCM decoction mJPYZ inhibited GC cells growth and EMT by reducing of glycolysis in PKM2 dependent manner. This evidence expanded our understanding of the anti-tumor mechanism of mJPYZ and further indicated mJPYZ a potential anti-tumor agent for GC patients.Chemical Compounds Studied in this ArticleRutin (PubChem CID: 5280805); Lobetyolin (PubChem CID: 53486204); Calycosin-7-glucoside (PubChem CID: 71571502); Formononetin (PubChem CID: 5280378); Calycosin (PubChem CID: 5280448); Ononin (PubChem CID: 442813); P-Coumaric Acid (PubChem CID: 637542).

scholarly journals Hexokinase 2 Regulates Ovarian Cancer Cell Migration, Invasion and Stemness via FAK/ERK1/2/MMP9/NANOG/SOX9 Signaling Cascades

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 813 ◽  
Author(s):  
Michelle K. Y. Siu ◽  
Yu-Xin Jiang ◽  
Jing-Jing Wang ◽  
Thomas H. Y. Leung ◽  
Chae Young Han ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Ovarian Cancer Cell ◽  
Lactate Production ◽  
Metabolic Reprogramming ◽  
Migration And Invasion ◽  
Hexokinase 2 ◽  
Cell Migration And Invasion

Metabolic reprogramming is a common phenomenon in cancers. Thus, glycolytic enzymes could be exploited to selectively target cancer cells in cancer therapy. Hexokinase 2 (HK2) converts glucose to glucose-6-phosphate, the first committed step in glucose metabolism. Here, we demonstrated that HK2 was overexpressed in ovarian cancer and displayed significantly higher expression in ascites and metastatic foci. HK2 expression was significantly associated with advanced stage and high-grade cancers, and was an independent prognostic factor. Functionally, knockdown of HK2 in ovarian cancer cell lines and ascites-derived tumor cells hindered lactate production, cell migration and invasion, and cell stemness properties, along with reduced FAK/ERK1/2 activation and metastasis- and stemness-related genes. 2-DG, a glycolysis inhibitor, retarded cell migration and invasion and reduced stemness properties. Inversely, overexpression of HK2 promoted cell migration and invasion through the FAK/ERK1/2/MMP9 pathway, and enhanced stemness properties via the FAK/ERK1/2/NANOG/SOX9 cascade. HK2 abrogation impeded in vivo tumor growth and dissemination. Notably, ovarian cancer-associated fibroblast-derived IL-6 contributed to its up-regulation. In conclusion, HK2, which is regulated by the tumor microenvironment, controls lactate production and contributes to ovarian cancer metastasis and stemness regulation via FAK/ERK1/2 signaling pathway-mediated MMP9/NANOG/SOX9 expression. HK2 could be a potential prognostic marker and therapeutic target for ovarian cancer.

scholarly journals Three-dimensional Traction Force Microscopy for Studying Cellular Interactions with Biomaterials

2012 ◽  
Vol 4 ◽  
pp. 144-150 ◽  
Author(s):  
J. Notbohm ◽  
J.-H. Kim ◽  
C. Franck ◽  
S. Maskarinec ◽  
D. Tirrell ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Traction Force ◽  
Traction Force Microscopy ◽  
Cellular Interactions ◽  
Force Microscopy

Application of 3D Traction Force Microscopy to Mechanotransduction of Cell Clusters

2011 ◽  
Vol 70 ◽  
pp. 21-27 ◽  
Author(s):  
Jacob Notbohm ◽  
Jin Hong Kim ◽  
Anand Asthagiri ◽  
Guruswami Ravichandran
Keyword(s):  
Finite Element ◽  
Three Dimensional ◽  
Traction Force ◽  
Two Dimensions ◽  
Three Dimensions ◽  
Cell Contact ◽  
Traction Force Microscopy ◽  
Inhibition Of Proliferation ◽  
Force Microscopy ◽  
Cell Clusters

With increasing understanding of the important role mechanics plays in cell behavior, the experimental technique of traction force microscopy has grown in popularity over the past decade. While researchers have assumed that cells on a flat substrate apply tractions in only two dimensions, a finite element simulation is discussed here that demonstrates how cells apply tractions in all three dimensions. Three dimensional traction force microscopy is then used to experimentally confirm the finite element results. Finally, the implications that the traction distributions of cell clusters have on the study of inhibition of proliferation due to cell contact and scattering of cells in a cluster are discussed.

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