Adriamycin-induced inhibition of melanoma cell invasion is correlated with decreases in tumor cell motility and increases in focal contact formation

1993 ◽  
Vol 11 (1) ◽  
pp. 91-102 ◽  
Author(s):  
Lillian A. Repesh ◽  
Sandra R. Drake ◽  
Mary C. Warner ◽  
Stephen W. Downing ◽  
Ronald Jyring ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Motility ◽  
Melanoma Cell ◽  
Cell Invasion ◽  
Focal Contact ◽  
Contact Formation ◽  
Tumor Cell Motility

scholarly journals PI3K therapy reprograms mitochondrial trafficking to fuel tumor cell invasion

2015 ◽  
Vol 112 (28) ◽  
pp. 8638-8643 ◽  
Author(s):  
M. Cecilia Caino ◽  
Jagadish C. Ghosh ◽  
Young Chan Chae ◽  
Valentina Vaira ◽  
Dayana B. Rivadeneira ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Motility ◽  
Cell Invasion ◽  
Mammalian Target Of Rapamycin ◽  
Membrane Dynamics ◽  
Tumor Cell Invasion ◽  
Transcriptional Reprogramming ◽  
Tumor Cell Motility ◽  
Molecular Therapies ◽  
Mitochondrial Trafficking

Molecular therapies are hallmarks of “personalized” medicine, but how tumors adapt to these agents is not well-understood. Here we show that small-molecule inhibitors of phosphatidylinositol 3-kinase (PI3K) currently in the clinic induce global transcriptional reprogramming in tumors, with activation of growth factor receptors, (re)phosphorylation of Akt and mammalian target of rapamycin (mTOR), and increased tumor cell motility and invasion. This response involves redistribution of energetically active mitochondria to the cortical cytoskeleton, where they support membrane dynamics, turnover of focal adhesion complexes, and random cell motility. Blocking oxidative phosphorylation prevents adaptive mitochondrial trafficking, impairs membrane dynamics, and suppresses tumor cell invasion. Therefore, “spatiotemporal” mitochondrial respiration adaptively induced by PI3K therapy fuels tumor cell invasion, and may provide an important antimetastatic target.

scholarly journals The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors

2006 ◽  
Vol 173 (3) ◽  
pp. 395-404 ◽  
Author(s):  
Weigang Wang ◽  
Ghassan Mouneimne ◽  
Mazen Sidani ◽  
Jeffrey Wyckoff ◽  
Xiaoming Chen ◽  
...  
Keyword(s):  
Cell Motility ◽  
Cell Invasion ◽  
Actin Polymerization ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Over Expression ◽  
Cell Biol ◽  
Tumor Cell Motility ◽  
New Strategies

Understanding the mechanisms controlling cancer cell invasion and metastasis constitutes a fundamental step in setting new strategies for diagnosis, prognosis, and therapy of metastatic cancers. LIM kinase1 (LIMK1) is a member of a novel class of serine–threonine protein kinases. Cofilin, a LIMK1 substrate, is essential for the regulation of actin polymerization and depolymerization during cell migration. Previous studies have made opposite conclusions as to the role of LIMK1 in tumor cell motility and metastasis, claiming either an increase or decrease in cell motility and metastasis as a result of LIMK1 over expression (Zebda, N., O. Bernard, M. Bailly, S. Welti, D.S. Lawrence, and J.S. Condeelis. 2000. J. Cell Biol. 151:1119–1128; Davila, M., A.R. Frost, W.E. Grizzle, and R. Chakrabarti. 2003. J. Biol. Chem. 278:36868–36875; Yoshioka, K., V. Foletta, O. Bernard, and K. Itoh. 2003. Proc. Natl. Acad. Sci. USA. 100:7247–7252; Nishita, M., C. Tomizawa, M. Yamamoto, Y. Horita, K. Ohashi, and K. Mizuno. 2005. J. Cell Biol. 171:349–359). We resolve this paradox by showing that the effects of LIMK1 expression on migration, intravasation, and metastasis of cancer cells can be most simply explained by its regulation of the output of the cofilin pathway. LIMK1-mediated decreases or increases in the activity of the cofilin pathway are shown to cause proportional decreases or increases in motility, intravasation, and metastasis of tumor cells.

GM3 Ganglioside Inhibits CD9-Facilitated Haptotactic Cell Motility:  Coexpression of GM3 and CD9 Is Essential in the Downregulation of Tumor Cell Motility and Malignancy†

Biochemistry ◽  
2001 ◽  
Vol 40 (21) ◽  
pp. 6414-6421 ◽  
Author(s):  
Masaya Ono ◽  
Kazuko Handa ◽  
Sandro Sonnino ◽  
Donald A. Withers ◽  
Hideo Nagai ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Motility ◽  
Tumor Cell Motility

scholarly journals Semaphorin 4D, a lymphocyte semaphorin, enhances tumor cell motility through binding its receptor, plexinB1, in pancreatic cancer

2011 ◽  
Vol 102 (11) ◽  
pp. 2029-2037 ◽  
Author(s):  
Shingo Kato ◽  
Kensuke Kubota ◽  
Takeshi Shimamura ◽  
Yoshiyasu Shinohara ◽  
Noritoshi Kobayashi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cell ◽  
Cell Motility ◽  
Semaphorin 4D ◽  
Tumor Cell Motility

scholarly journals Fibroblasts modulate the tumor cell motility and their mTOR/S6K1 phosphorylation status in vitro

2019 ◽  
Vol 35 (6) ◽  
pp. 417-426
Author(s):  
N. Ya. Hotsuliak ◽  
V. V. Kosach ◽  
I. O. Tykhonkova ◽  
S. S. Palchevskii ◽  
A. I. Khoruzhenko
Keyword(s):  
Tumor Cell ◽  
Cell Motility ◽  
Tumor Cell Motility

Tumor Cell Motility and Invasion

2002 ◽  
pp. 467-473 ◽  
Author(s):  
J. Jouanneau ◽  
J.P. Thiery
Keyword(s):  
Tumor Cell ◽  
Cell Motility ◽  
Tumor Cell Motility

Abstract 1039: A Proprotein Convertase Regulates Integrin - MMP Cooperation In VSMCs

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Philipp Stawowy ◽  
Heike Meyborg ◽  
Bernadette Baumann ◽  
Dietger Stibenz ◽  
Eckart Fleck ◽  
...  
Keyword(s):  
Cell Motility ◽  
Focal Contact ◽  
Proprotein Convertase ◽  
Membrane Expression ◽  
Ecm Remodeling ◽  
Matrigel Invasion ◽  
Contact Formation ◽  
Mmp Inhibitor ◽  
Endoproteolytic Cleavage ◽  
Alpha V Beta 3

ECM remodeling is a key feature in atherosclerosis and restenosis. Integrins link the cytoskeleton with the ECM and regulate adhesion/migration. MMPs are the major degrading enzymes important for cell motility. Binding of the MMP-2 zymogen to alpha v beta 3 is necessary for its full activation, thereby coordinating cell motility with membrane-associated proteolysis. The alpha v integrin chain is synthesized as a proprotein that is endoproteolytically activated by furin. Furin is the prototype proprotein convertase, highly expressed in human atherosclerotic lesions. The aim of this study was to investigate the role of furin in integrin -MMP coordination and cooperation in VSMCs. Methods and Results: Treatment of VSMCs with either the furin inhibitor dec-CMK (50 umol/L) or an MMP-inhibitor (GM6001; 25 umol/L) significantly inhibited VSMC Matrigel invasion (p<0.05 vs. controls). Immunoblotting demonstrated that dec-CMK inhibited alpha v endoproteolytic activation, but this did not affect alpha v membrane expression assessed by FACS analysis. Zymography revealed that in dec-CMK or TSR1265 (10 umol/L; an inhibitor of MMP-2 binding to alpha v beta 3) treated cells, maturation of the intermediate 68 kDa MMP-2 to its fully active 62 kDa form was significantly decreased (p<0.05 vs. controls). Furthermore, dec-CMK significantly inhibited binding of FITC-conjugated pro-MMP-2 to the cell surface of VSMCs. Immunfluorescence and 3D in gel zymography demonstrated that inhibition of endoproteolytic cleavage of the alpha v integrin inhibits actin rearrangement and focal contact formation upon integrin stimulation (matrix adhesion or PMA treatment), as well as membrane-associated proteolysis. Conclusion: Our study demonstrates that endoproteolytic cleavage of alpha v integrin by furin regulates not only integrin activation, but also affects MMP-2 maturation. Endoproteolytic activation of alpha v is required for cytoskeleton rearrangement upon integrin stimulation and focal contact formation, as well as the coordination and cooperation of integrins and MMPs. Therefore furin-convertase may be a novel target in atherosclerosis and restenosis.

scholarly journals Intravital Imaging of Tumor Cell Motility in the Tumor Microenvironment Context

2018 ◽  
pp. 175-193 ◽  
Author(s):  
Battuya Bayarmagnai ◽  
Louisiane Perrin ◽  
Kamyar Esmaeili Pourfarhangi ◽  
Bojana Gligorijevic
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Cell Motility ◽  
Intravital Imaging ◽  
Tumor Cell Motility
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