Heterotrimeric G protein signaling in cancer cells with regard to metastasis formation

Entschladen, Frank; Zänker, Kurt S.; Powe, Desmond G.

doi:10.4161/cc.10.7.15208

Cited by 20 publications

(8 citation statements)

References 84 publications

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“…One mechanism by which dynamic microtubules may regulate migration is through their interactions with the Gproteins associated with focal adhesions. The actin and microtubule cytoskeletons interact with small GTPases of the Rho family (Rho A, Rac1, and Cdc42) [Entschladen et al, 2000;Ridley, 2006;Watanabe et al, 2005]. Our data suggest that the direction and rate of cell migration may be regulated by dynamic microtubules that target focal adhesions and that regulate the formation or disassembly of focal adhesions via regulation of Rho and Rac activity.…”

Section: Suppression Of Dynamic Instabilitymentioning

confidence: 80%

Mechanisms of inhibition of endothelial cell migration by taxanes

et al. 2013

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Several antiangiogenic mechanisms have been proposed for the widely-used cancer chemotherapeutic drugs taxotere (docetaxel) and taxol (paclitaxel), but none has been definitively identified. We analyzed their effects at a range of concentrations on migration and mitosis of human umbilical vein endothelial cells (HUVECs) on microtubule and focal adhesion morphology and microtubule dynamic instability during migration. Both taxanes inhibited migration by inhibiting both maintenance of the forward direction of the cell and by slowing migration over the entire contorted path length. At low (but not all) taxane concentrations that inhibit HUVEC migration, the shortening rates and shortening lengths of microtubules at the leading edge were strongly inhibited; peripheral microtubules were reduced in number and fewer targeted focal adhesions; focal adhesions doubled in length and became ring-shaped, elongate, and reduced in number; and an increase in stabilized microtubules occurred centrally. HUVEC migration was 13-19-fold more sensitive to taxanes than was mitosis confirming that taxanes exhibit significant effects in addition to mitotic arrest that may contribute to their overall antitumor effects. No relationship was detected between centrosome position and migration characteristics. The data suggest that taxanes inhibit migration, at least in part, by inhibiting the dynamic instability of microtubules that possibly interact with guanine nucleotide exchange factors and thus with the focal adhesion-associated G-proteins that then lead to disruption of the regulated formation and turnover of focal adhesions. A mechanism is presented by which subcytotoxic concentrations of taxanes might stabilize dynamic instability of a few microtubules and thereby inhibit migration and angiogenesis.

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Section: Suppression Of Dynamic Instabilitymentioning

confidence: 80%

Mechanisms of inhibition of endothelial cell migration by taxanes

et al. 2013

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“…Go is also required for the proper development and functioning of the heart [109,110]. In addition to the crucial developmental and physiological functions of this G protein [111,112], it also has important pathological implications, especially in cancer [113]. Constitutive activation of Gao induced transformation in NIH-3T3 fibroblasts and tumors in mouse xenografts [114,115].…”

Section: The Heterotrimeric Go Protein: Captain and His Crewmentioning

confidence: 99%

Yellow submarine of the Wnt/Frizzled signaling: Submerging from the G protein harbor to the targets

Koval

Purvanov

Egger-Adam

et al. 2011

Biochemical Pharmacology

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“…These heterotrimers are linked to specific receptors, denominated as G protein-coupled receptors (GPCR) which sense different ligands such as hormones, odor, growth factors, and even photons (Beckerman 2005). After that, the subunits of the heterotrimers activate downstream cellular protein effectors that ultimately elicit changes in cell metabolism (McCudden et al 2005;Entschladen et al 2011).…”

Section: Introductionmentioning

confidence: 99%