The Role of Microtubules and Their Dynamics in Cell Migration

Ganguly, Anutosh; Yang, Hailing; Sharma, Ritu; Patel, Kamala D.; Cabral, Fernando

doi:10.1074/jbc.m112.423905

Cited by 112 publications

(94 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These findings led us to conclude that fisetin is indeed a microtubule interfering agent that suppresses the microtubules which in turn led to reduction in cell migration. A parallel conclusion was previously reported that low drug concentrations in various cell lines do not affect mitosis yet inhibit motility [29], as well as by experiments showing that inhibition of cell migration by antimitotic drugs is due to their suppression of microtubule dynamics rather than to some other drug effects [30,31]. …”

Section: Discussionsupporting

confidence: 79%

Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells

et al. 2015

View full text Add to dashboard Cite

Microtubule targeting based therapies have revolutionized cancer treatment; however, resistance and side effects remain a major limitation. Therefore, novel strategies that can overcome these limitations are urgently needed. We made a novel discovery that fisetin, a hydroxyflavone, is a microtubule stabilizing agent. Fisetin binds to tubulin and stabilizes microtubules with binding characteristics far superior than paclitaxel. Surface plasmon resonance and computational docking studies suggested that fisetin binds to β-tubulin with superior affinity compared to paclitaxel. Fisetin treatment of human prostate cancer cells resulted in robust up-regulation of microtubule associated proteins (MAP)-2 and -4. In addition, fisetin treated cells were enriched in α-tubulin acetylation, an indication of stabilization of microtubules. Fisetin significantly inhibited PCa cell proliferation, migration, and invasion. Nudc, a protein associated with microtubule motor dynein/dynactin complex that regulates microtubule dynamics, was inhibited with fisetin treatment. Further, fisetin treatment of a P-glycoprotein overexpressing multidrug-resistant cancer cell line NCI/ADR-RES inhibited the viability and colony formation. Our results offer in vitro proof-of-concept for fisetin as a microtubule targeting agent. We suggest that fisetin could be developed as an adjuvant for treatment of prostate and other cancer types.

show abstract

Section: Discussionsupporting

confidence: 79%

Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells

et al. 2015

View full text Add to dashboard Cite

show abstract

“…These data further reinforce the role of Rab7a in migration and explain previous data indicating that Rab7a depletion causes a decrease, but not a complete inhibition, of vimentin phosphorylation at various sites accompanied by an increase of insoluble (filamentous) vimentin [17]. In support of this, it has been previously demonstrated that alterations of cytoskeleton components dynamics affect cell migration [75]. Notably, Rac1 and vimentin functions are connected [51][52][53][54].…”

Section: Discussionsupporting

confidence: 77%

Rab7a regulates cell migration through Rac1 and vimentin

Margiotta

Progida

Bakke

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

Rab7a, a small GTPase of the Rab family, is localized to late endosomes and controls late endocytic trafficking. The discovery of several Rab7a interacting proteins revealed that Rab7a function is closely connected to cytoskeletal elements. Indeed, Rab7a recruits on vesicles RILP and FYCO that are responsible for the movement of Rab7a-positive vesicles and/or organelles on microtubule tracks, but also directly interacts with Rac1, a fundamental regulator of actin cytoskeleton, and with peripherin and vimentin, two intermediate filament proteins. Considering all these interactions and, in particular, the fact that Rac1 and vimentin are key factors for cellular motility, we investigated a possible role of Rab7a in cell migration. We show here that Rab7a is needed for cell migration as Rab7a depletion causes slower migration of NCI H1299 cells affecting cell velocity and directness.Rab7a depletion negatively affects adhesion and spreading onto fibronectin substrates, altering β1-integrin activation, localization and intracellular trafficking, and myosin X localization. In fact, Rab7a-depleted cells show 40% less filopodia and active integrin accumulates at the leading edge of migrating cells. Furthermore, Rab7a depletion decreases the amount of active Rac1 but not its abundance and reduces the number of cells with vimentin filaments facing the wound, indicating that Rab7a has a role in the orientation of vimentin filaments during migration. In conclusion, our results demonstrate a key role of Rab7a in the regulation of different aspects of cell migration.

show abstract

“…On 2D surfaces, we would expect similar oscillations around the cell perimeter upon the disassembly of microtubules. However, the lack of synchronization of oscillations around the perimeter would cause the cell as a whole to undergo only short-range random walks, as reported in the literature (56,57). We would expect similar oscillations for cells migrating in confined 3D environments such as narrow channels.…”

Section: Discussionmentioning

confidence: 70%

“…Taxol-stabilized microtubules may also be defective in their interactions with other structures such as focal adhesions to affect the production of excitation and/or inhibitory signals. In addition, although nocodazole allows an anterior end to turn into a retracting posterior end during oscillation, Taxolinduced stabilization of microtubules has been shown to block cell retraction (57), which may be sufficient to prevent oscillatory migration.…”

Section: Discussionmentioning

confidence: 99%

Microtubules stabilize cell polarity by localizing rear signals

Zhang

Guo

Wang

2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Microtubules are known to play an important role in cell polarity; however, the mechanism remains unclear. Using cells migrating persistently on micropatterned strips, we found that depolymerization of microtubules caused cells to change from persistent to oscillatory migration. Mathematical modeling in the context of a local-excitation–global-inhibition control mechanism indicated that this mechanism can account for microtubule-dependent oscillation, assuming that microtubules remove inhibitory signals from the front after a delayed generation. Experiments further supported model predictions that the period of oscillation positively correlates with cell length and that oscillation may be induced by inhibiting retrograde motors. We suggest that microtubules are required not for the generation but for the maintenance of cell polarity, by mediating the global distribution of inhibitory signals. Disassembly of microtubules induces cell oscillation by allowing inhibitory signals to accumulate at the front, which stops frontal protrusion and allows the polarity to reverse.

show abstract

The Role of Microtubules and Their Dynamics in Cell Migration

Cited by 112 publications

References 38 publications

Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells

Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells

Rab7a regulates cell migration through Rac1 and vimentin

Microtubules stabilize cell polarity by localizing rear signals

Contact Info

Product

Resources

About