ARF1 controls Rac1 signaling to regulate migration of MDA-MB-231 invasive breast cancer cells

Lewis-Saravalli, Sebastian; Campbell, Shirley; Claing, Audrey

doi:10.1016/j.cellsig.2013.05.011

Cited by 40 publications

(38 citation statements)

References 24 publications

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“…20–22 Arf1 promotes binding of POR1 to membranes and also promotes the activation of Rac1 through the GIT/PIX complex. 24 GIT is the GTPase-activating protein (GAP) for Arf and is responsible for the conversion of Arf-GTP to Arf-GDP.…”

Section: Discussionmentioning

confidence: 99%

Geometry sensing through POR1 regulates Rac1 activity controlling early osteoblast differentiation in response to nanofiber diameter

2015

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Bone grafting procedures in the United States rely heavily upon autografts and allografts, which are donor-dependent, cause donor site pain, and can transmit disease. Synthetic bone grafts can reduce these risks; however, synthetics lack the bone differentiating (osteoinductive) abilities of auto- and allografts. Achieving innate osteoinductive properties of synthetics through surface modifications is currently under investigation. This study focuses on nanofibers, with emphasis on how fiber diameter and the potential curvature sensor POR1 affect the activation of the signalingmoleculesRac1 and Arf1, and leading to expression of alkaline phosphatase (ALP), an osteoinductive marker. Diameters of 0.1, 0.3, and 1.0 μm were compared against a flat control. The highest level of Rac1 activation was achieved on the smallest fibers (0.1 μm), a trend that was long in POR1 knockdowns. This supports the hypothesis that on small nanofibers, POR1 favorably binds to highly curved cell membranes, which allows Rac1 to subsequently dissociate and activate. When the curvature is insufficient to bind POR1, POR1 binds to inactive Rac1 and competitively inhibits its activation. Arf1 activation followed an opposite trend, with the largest nanofibers exhibiting the highest activity. This trend reinforces the known interaction between Rac1 and Arf1 through the GIT/PIX complex, an Arf1 GAP and Rac1 GEF, respectively. Large, (1.0μm), nanofibers demonstrated the highest ALP activity, indicating that ALP expression is inversely dependent on Rac1 activation. Knockdown of POR1 resulted in increased ALP activity across the substrates but without regard to the curvature sensing trend seen previously. Thus, POR1 senses curvature and increases Rac1 activity, which negatively regulates bone differentiation.

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Section: Discussionmentioning

confidence: 99%

Geometry sensing through POR1 regulates Rac1 activity controlling early osteoblast differentiation in response to nanofiber diameter

2015

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“…We show that Rab7b triggers myosin II activation by stimulating phosphorylation of residue Ser19 of MLC, through the activation of RhoA, revealing that a Rab protein modulates the activity of another family of small GTP-binding proteins, the Rho family. Interestingly, other small GTPases, Arf1 and Arf6, known to regulate endosomal transport (Kobayashi and Fukuda, 2013;Nakai et al, 2013;Hongu and Kanaho, 2014), also control cytoskeletal organization through crosstalk with Rho-family GTPases (Lewis-Saravalli et al, 2013;Schlienger et al, 2014). Although the exact mechanism of Rho activation remains to be elucidated, it could occur in several ways, such as through the recruitment of Guanine nucleotide exchange factors (GEFs) or the downregulation of Rho GTPase-activating proteins (GAPs).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, an additional function for the Arf family has been identified recently. Indeed, members of this family are also regulators of actin remodeling and cell migration (Myers and Casanova, 2008;Lewis-Saravalli et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

A novel interaction between Rab7b and actomyosin reveals a dual role in intracellular transport and cell migration

Borg

Bakke

Progida

2014

Journal of Cell Science

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Rab proteins are small GTPases that regulate transport between the different compartments of the endomembrane system in eukaryotic cells. Here, we show that Rab7b, a Rab that controls the transport between late endosomes and the trans Golgi network, interacts directly with myosin II. We illustrate the functional relevance of this interaction, demonstrating that myosin II mediates the transport of Rab7b endosomes, as Rab7b dynamics are strongly affected after myosin II depletion or inhibition. We also demonstrate that a member of the Rab family regulates actin remodeling and, consequently, influences cell adhesion, polarization and migration. We find the molecular mechanism by which Rab7b influences stress fiber formationthrough controlling the activation status of the small GTPase RhoA and therefore influencing myosin light chain phosphorylation. Our findings reveal a newly identified role for Rab proteins outside of their canonical role in intracellular trafficking, identifying Rab7b as a coordinator of cytoskeletal organization.

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“…The quantifications of each experiment are presented as fold-increase over basal, are normalized to total protein content, and are the mean Ϯ S.E. with (***) p Ͻ 0.001. p66Shc and Grb2 Regulate EGFR-dependent Activation of ARF FEBRUARY 28, 2014 • VOLUME 289 • NUMBER 9 was a downstream effector of ARF1 signals in MDA-MB-231 cells and the overexpression of a constitutively active form of Rac1 could reverse the inhibitory effect of ARF1 depletion on cell migration (50). Therefore, p66Shc may promote cell migration via the activation of Rac1.…”

Section: P66shc and Grb2 Regulate Egfr-dependent Activation Of Arfmentioning

confidence: 99%

The Adaptor Proteins p66Shc and Grb2 Regulate the Activation of the GTPases ARF1 and ARF6 in Invasive Breast Cancer Cells

Haines

Saucier

Claing

2014

Journal of Biological Chemistry

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Background: ADP-ribosylation factors (ARF) 1 and 6 play an important role in breast cancer cell proliferation, migration, and invasion. Results: In invasive breast cancer cells, EGF-mediated ARF1 and ARF6 activation is regulated by p66Shc and Grb2. Conclusion: Adaptor proteins are required to promote ARF activation. Significance: Understanding the signaling mechanisms leading to ARF activation may identify novel therapeutic targets for the treatment of breast cancer.

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ARF1 controls Rac1 signaling to regulate migration of MDA-MB-231 invasive breast cancer cells

Cited by 40 publications

References 24 publications

Geometry sensing through POR1 regulates Rac1 activity controlling early osteoblast differentiation in response to nanofiber diameter

Geometry sensing through POR1 regulates Rac1 activity controlling early osteoblast differentiation in response to nanofiber diameter

A novel interaction between Rab7b and actomyosin reveals a dual role in intracellular transport and cell migration

The Adaptor Proteins p66Shc and Grb2 Regulate the Activation of the GTPases ARF1 and ARF6 in Invasive Breast Cancer Cells

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