EGF-stimulated activation of Rab35 regulates RUSC2–GIT2 complex formation to stabilize GIT2 during directional lung cancer cell migration

Duan, Biao; Cui, Jie; Sun, Shixiu; Zheng, Jie; Zhang, Yujie; Ye, Bixing; Yan, Chen; Deng, Wenjie; Du, Jie; Zhu, Yichao; Chen, Yongchang; Gu, Luo

doi:10.1016/j.canlet.2016.05.027

Cited by 28 publications

(37 citation statements)

References 62 publications

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“…Conversely, Rab35 activation after prolonged EGF stimulation reduces the interaction between the G protein‐coupled receptor kinase interacting ARFGAP 2 (GIT2) and its binding partner RUSC2 and consequently reduces directional cell migration in non‐small cell lung cancer (NSCLC) . However, contrary to the studies mentioned above, Rab35 activation downstream of Wnt5 signaling promotes cell migration in breast cancer MCF‐7 cells via a Dvl2/Rab35/Rac1 signaling pathway, perhaps due to additional dominant effects downstream of Wnt5.…”

Section: Rab35 In Cell Migrationmentioning

confidence: 92%

Rab35 GTPase and cancer: Linking membrane trafficking to tumorigenesis

Shaughnessy

Échard

2018

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Rab35 is a small GTPase that is involved in many cellular processes, including membrane trafficking, cell polarity, lipid homeostasis, immunity, phagocytosis and cytokinesis. Recent studies showed that activating mutations confer Rab35 with oncogenic properties. Conversely, downregulation of Rab35 inverts apico-basal cell polarity and promotes cell migration. Here we review Rab35's known functions in membrane trafficking and signaling, cell division and cell migration in cancer cells and discuss the importance of Rab35-dependent membrane trafficking in cancer progression.

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Section: Rab35 In Cell Migrationmentioning

confidence: 92%

Rab35 GTPase and cancer: Linking membrane trafficking to tumorigenesis

Shaughnessy

Échard

2018

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“…Immunofluorescent was performed as previously described [22]. Briefly, cells were treated with or without 100 nM Ang-II for the time indicated after serum starvation overnight, fixed in ice-cold 4% paraformaldehyde (PFA) for 20min, rinsed with phosphate-buffered saline (PBS) for three times and permeabilized with 0.1% Triton X-100 before blocking in 1% BSA for 1 h. The cells were incubated with primary antibodies at 4°C overnight, and then incubated with secondary antibodies for 1.5h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Enhanced expression and phosphorylation of Sirt7 activates smad2 and ERK signaling and promotes the cardiac fibrosis differentiation upon angiotensin-II stimulation

Wang

Liu

et al. 2017

PLoS ONE

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Cardiac fibroblasts (CFs) phenotypic conversion to myofibroblasts (MFs) represents a crucial event in cardiac fibrosis that leads to impaired cardiac function. However, regulation of this phenotypic transformation remains unclear. Here, we showed that sirtuin-7 (Sirt7) plays an important role in the regulation of MFs differentiation. Sirt7 expression and phosphorylation were upregulated in CFs upon angiotensin-II (Ang-II) stimulation. Sirt7 depletion by siRNA in CFs resulted in decreased cell proliferation and extracellular matrix (ECM) deposition. Further, examination of Sirt7-depleted CFs demonstrated significantly lower expression of α-smooth muscle actin (α-SMA), the classical marker of MFs differentiation, and decreased formation of focal adhesions. Moreover, overexpression of Sirt7 increased α-SMA expression in Ang-II treated CFs and exacerbated Ang-II-induced MFs differentiation. Moreover, Sirt7 depletion could largely reverse Ang-II induced increase of nuclear translocalization and activity of smad2 and extracellular regulated kinases (ERK) in CFs. Importantly, the increased differentiation of CFs to MFs was also abolished by smad2 siRNA or U0126. Our findings reveal a novel role of Sirt7 and its phosphorylation in the phenotypic conversion of CFs to MFs and might lead to the development of new therapeutic and prognostic tools for cardiac fibrosis.

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“…Rab35 plays an important role in non-small cell lung cancer (NSCLC) cell migration by regulating the interaction of RUSC2 (Rab35 effector protein) and GIT2 (Arf6-GAP) [58]. Both RUSC2 and GITS2 have been found to regulate cell polarity and directional cell migration [16,59].…”

Section: Rab35 Functions In Cell Migration and Cancersmentioning

confidence: 99%

“…GIT2 interacts with paxillin to mediate normal cell spreading and lamellipodia formation [61]. Upon EGF stimulation, Rab35 is activated and promotes the binding of RUSC2 to the non-phosphorylated form of GIT2 [58]. Knockdown of Rab35 or RUSC2 by RNAi resulted in decreased GIT2 phosphorylation and its half-life, indicating that Rab35 and RUSC2 are each essential for GIT2 phosphorylation and stability [58].…”

Section: Rab35 Functions In Cell Migration and Cancersmentioning

confidence: 99%

“…Upon EGF stimulation, Rab35 is activated and promotes the binding of RUSC2 to the non-phosphorylated form of GIT2 [58]. Knockdown of Rab35 or RUSC2 by RNAi resulted in decreased GIT2 phosphorylation and its half-life, indicating that Rab35 and RUSC2 are each essential for GIT2 phosphorylation and stability [58]. The phosphorylated form of GIT2 is released from RUSC2 and localizes to the plasma membrane to mediate cell migration [58].…”

Section: Rab35 Functions In Cell Migration and Cancersmentioning

confidence: 99%

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The Function of Rab35 in Development and Disease

Song¹,

Testa²

2018

Peripheral Membrane Proteins

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Rab35 mediates membrane trafficking between the plasma membrane and the early endosomes at the cell surface. Our understanding of the cellular function of Rab35 reveals its role in development and diseases. In the developmental context, Rab35 has been shown to play an important role in regulating epithelial polarity, lumen opening, myoblast fusion, intercalation of epithelium, myelination, neurite outgrowth, and oocyte meiotic maturation. Disruption of recycling endosome mediated by Rab35 has been linked to several neurological diseases, including Parkinson's disease and Down syndrome. In addition, because Rab35 modulates cell migration through its interaction with various effectors, Rab35 plays an important role in cancers. Lastly, the Rab35-mediated recycling endosomal pathway and exocytosis is utilized by pathogens or hijacked by pathogens to promote their infection and survival. This review summarizes the function of Rab35 in endocytosis and focuses on the role of Rab35 in the context of development and diseases.

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EGF-stimulated activation of Rab35 regulates RUSC2–GIT2 complex formation to stabilize GIT2 during directional lung cancer cell migration

Cited by 28 publications

References 62 publications

Rab35 GTPase and cancer: Linking membrane trafficking to tumorigenesis

Rab35 GTPase and cancer: Linking membrane trafficking to tumorigenesis

Enhanced expression and phosphorylation of Sirt7 activates smad2 and ERK signaling and promotes the cardiac fibrosis differentiation upon angiotensin-II stimulation

The Function of Rab35 in Development and Disease

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