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Open AccessJournal ArticleDOI

Rho GTPases are over‐expressed in human tumors

TLDR
Overall, increase in the amount of Rho GTPases, in particular RhoA, appears to be a frequent event in different types of human tumors, which supports the view that RhoGTPases are involved in human carcinogenesis.
Abstract
Small GTPases of the Rho family are involved in the regulation of a variety of cellular processes, such as the organization of the microfilamental network, cell-cell contact and malignant transformation. To address the question of whether Rho proteins are involved in carcinogenesis in man, we compared their expression in tumors from colon, breast and lung with that of the corresponding normal tissue originating from the same patient. As shown by Rho-specific 32P-ADP-ribosylation, as well as Western-blot analysis, the amount of RhoA protein was largely increased in all 3 types of tumors tested. The most dramatic differences in the expression of Rho GTPases were observed in breast tissue. All breast tumors analyzed showed high levels of RhoA, Rac and Cdc42 proteins, whereas in the corresponding normal tissue these Rho proteins were hardly or not detectable. Progression of breast tumors from WHO grade I to grade III was accompanied by a significant average increase in RhoA protein. Overall, increase in the amount of Rho GTPases, in particular RhoA, appears to be a frequent event in different types of human tumors. This supports the view that Rho GTPases are involved in human carcinogenesis. Int. J. Cancer 81:682–687, 1999. © 1999 Wiley-Liss, Inc.

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Journal ArticleDOI

Tensional homeostasis and the malignant phenotype.

TL;DR: It is found that tumors are rigid because they have a stiff stroma and elevated Rho-dependent cytoskeletal tension that drives focal adhesions, disrupts adherens junctions, perturbs tissue polarity, enhances growth, and hinders lumen formation.
Journal ArticleDOI

RHO-GTPases and cancer.

TL;DR: The RAS oncogenes are members of a large family of small GTPases that bind GTP and hydrolyse it to GDP and the switching between these two states regulates a wide range of cellular processes.
Journal ArticleDOI

Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis

TL;DR: Two modes of tumour-cell motility in 3D matrices that involve different usage of Rho signalling are identified and combined blockade of extracellular proteases and ROCK negates the ability of tumours to switch between modes of motility and synergises to prevent tumour cell invasion.
Journal ArticleDOI

Rational design and characterization of a Rac GTPase-specific small molecule inhibitor

TL;DR: A first-generation small-molecule inhibitor of Rac GTPase targeting Rac activation by GEF, identified by a structure-based virtual screening of compounds that fit into a surface groove of Rac1 known to be critical for GEF specification, is reported.
Journal ArticleDOI

Mammalian G proteins and their cell type specific functions

TL;DR: In this review, some of the functions of heterotrimeric G proteins in defined cells and tissues are described.
References
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Journal ArticleDOI

p53 mutations in human cancers

TL;DR: The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues as mentioned in this paper.
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Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia

TL;DR: It is reported here that cdc42, another member of the rho family, triggers the formation of a third type of actin-based structure found at the cell periphery, filopodia, in addition to stress fibers, and rho controls the assembly of focal adhesion complexes.
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Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase).

TL;DR: The phosphorylation of MLC by Rho-kinase resulted in the facilitation of the actin activation of myosin ATPase, which may partly account for the mechanism by which Rho regulates cytokinesis, cell motility, or smooth muscle contraction.
Journal ArticleDOI

The small GTP-binding proteins Rac1 and Cdc42regulate the activity of the JNK/SAPK signaling pathway

TL;DR: It is shown that in COS-7 cells, activated Ras effectively stimulates MAPK but poorly induces JNK activity, which strongly support a critical role for Rac1 and Cdc42 in controlling the JNK signaling pathway.
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An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G1

TL;DR: When microinjected into quiescent fibroblasts, Rho, Rac, and Cdc42 stimulated cell cycle progression through G1 and subsequent DNA synthesis, and microinjection of dominant negative forms of Rac and CDC42 or of the Rho inhibitor C3 transferase blocked serum-induced DNA synthesis.
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