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 Tumor Cell Invasion in Glioblastoma

2020 ◽  
Vol 21 (6) ◽  
pp. 1932 ◽  
Author(s):  
Arabel Vollmann-Zwerenz ◽  
Verena Leidgens ◽  
Giancarlo Feliciello ◽  
Christoph A. Klein ◽  
Peter Hau
Keyword(s):  
Tumor Cell ◽  
Cell Invasion ◽  
Treatment Resistance ◽  
Tumor Cell Invasion ◽  
Surrounding Tissue ◽  
Glioma Invasion ◽  
Curative Therapy ◽  
New Therapeutic Approaches ◽  
Invasion Mechanisms ◽  
Tumor Cell Motility

Glioblastoma (GBM) is a particularly devastating tumor with a median survival of about 16 months. Recent research has revealed novel insights into the outstanding heterogeneity of this type of brain cancer. However, all GBM subtypes share the hallmark feature of aggressive invasion into the surrounding tissue. Invasive glioblastoma cells escape surgery and focal therapies and thus represent a major obstacle for curative therapy. This review aims to provide a comprehensive understanding of glioma invasion mechanisms with respect to tumor-cell-intrinsic properties as well as cues provided by the microenvironment. We discuss genetic programs that may influence the dissemination and plasticity of GBM cells as well as their different invasion patterns. We also review how tumor cells shape their microenvironment and how, vice versa, components of the extracellular matrix and factors from non-neoplastic cells influence tumor cell motility. We further discuss different research platforms for modeling invasion. Finally, we highlight the importance of accounting for the complex interplay between tumor cell invasion and treatment resistance in glioblastoma when considering new therapeutic approaches.

scholarly journals Myc Regulation of a Mitochondrial Trafficking Network Mediates Tumor Cell Invasion and Metastasis

2019 ◽  
Vol 39 (14) ◽  
Author(s):  
Ekta Agarwal ◽  
Brian J. Altman ◽  
Jae Ho Seo ◽  
Irene Bertolini ◽  
Jagadish C. Ghosh ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Invasion ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Adapter Protein ◽  
Aggressive Cancer ◽  
Tumor Cell Motility ◽  
Myc Gene ◽  
Mitochondrial Trafficking ◽  
Cortical Cytoskeleton

ABSTRACT The Myc gene is a universal oncogene that promotes aggressive cancer, but its role in metastasis has remained elusive. Here, we show that Myc transcriptionally controls a gene network of subcellular mitochondrial trafficking that includes the atypical mitochondrial GTPases RHOT1 and RHOT2, the adapter protein TRAK2, the anterograde motor Kif5B, and an effector of mitochondrial fission, Drp1. Interference with this pathway deregulates mitochondrial dynamics, shuts off subcellular organelle movements, and prevents the recruitment of mitochondria to the cortical cytoskeleton of tumor cells. In turn, this inhibits tumor chemotaxis, blocks cell invasion, and prevents metastatic spreading in preclinical models. Therefore, Myc regulation of mitochondrial trafficking enables tumor cell motility and metastasis.

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 CD155/PVR plays a key role in cell motility during tumor cell invasion and migration

BMC Cancer ◽  
2004 ◽  
Vol 4 (1) ◽  
Author(s):  
Kevin E Sloan ◽  
Brenda K Eustace ◽  
Jean K Stewart ◽  
Carol Zehetmeier ◽  
Claudia Torella ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Motility ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
Invasion And Migration ◽  
And Migration

CUTL1–a modulator of tumor cell invasion and target of TGF-beta which is highly expressed in colon cancer

2004 ◽  
Vol 42 (08) ◽  
Author(s):  
P Michl ◽  
M Ei'Bahrawy ◽  
R Poulsom ◽  
A Ramjaun ◽  
J Downward
Keyword(s):  
Colon Cancer ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
Tgf Beta

Tumor Cell Invasion Assay

BIO-PROTOCOL ◽  
2012 ◽  
Vol 2 (3) ◽  
Author(s):  
Yanling Chen
Keyword(s):  
Tumor Cell ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
Invasion Assay

scholarly journals Regulation of CD44 Alternative Splicing by SRm160 and Its Potential Role in Tumor Cell Invasion

2006 ◽  
Vol 26 (1) ◽  
pp. 362-370 ◽  
Author(s):  
Chonghui Cheng ◽  
Phillip A. Sharp
Keyword(s):  
Alternative Splicing ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Rna Splicing ◽  
Tumor Cell Invasion ◽  
Dependent Manner ◽  
Cd44 Isoforms ◽  
Transmembrane Glycoprotein ◽  
Cell Invasiveness ◽  
Interfering Rna

ABSTRACT The multiple isoforms of the transmembrane glycoprotein CD44 are produced by alternative RNA splicing. Expression of CD44 isoforms containing variable 5 exon (v5) correlates with enhanced malignancy and invasiveness of some tumors. Here we demonstrate that SRm160, a splicing coactivator, regulates CD44 alternative splicing in a Ras-dependent manner. Overexpression of SRm160 stimulates inclusion of CD44 v5 when Ras is activated. Conversely, small interfering RNA (siRNA)-mediated silencing of SRm160 significantly reduces v5 inclusion. Immunoprecipitation shows association of SRm160 with Sam68, a protein that also stimulates v5 inclusion in a Ras-dependent manner, suggesting that these two proteins interact to regulate CD44 splicing. Importantly, siRNA-mediated depletion of CD44 v5 decreases tumor cell invasion. Reduction of SRm160 by siRNA transfection downregulates the endogenous levels of CD44 isoforms, including v5, and correlates with a decrease in tumor cell invasiveness.

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