Oxidative stress enhances Axl-mediated cell migration through an Akt1/Rac1-dependent mechanism

Huang, Jhy Shrian; Cho, Chun Yu; Hong, Chih Chen; Yan, Ming; Hsieh, Mao‐Chih; Lay, Jong Ding; Lai, Gi Ming; Cheng, Ann‐Lii; Chuang, Shuang‐En

doi:10.1016/j.freeradbiomed.2013.09.011

Cited by 48 publications

(37 citation statements)

References 63 publications

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“…Since the reduction in migration that is mediated by p62 can be rescued by the knockdown of NQO1, this further supports a role for the miR-372 -p62-NQO1 cascade in the progression of HNSCC. Various lines of evidence support the hypothesis that ROS may participate in the regulation of Rho family members and modulate cytoskeletal organization or that ROS may activate other signals to increase migration [41, 48]. NQO1 was reported to attenuate ROS and the proliferation of vascular endothelial cells [49].…”

Section: Discussionmentioning

confidence: 99%

miR-372inhibits p62 in head and neck squamous cell carcinomain vitroandin vivo

Yeh¹,

Liu

Wong

et al. 2015

Oncotarget

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Here we showed that exogenous miR-372 expression and knockdown of p62 (sequestosome1 or SQSTM1), both increased migration of head and neck squamous cell carcinoma (HNSCC) cells. p62 induced phase II detoxification enzyme NADPH quinone oxidoreductase 1 (NQO1), which decreased ROS levels and cell migration. Also, miR-372 decreased p62 during hypoxia, thus increasing cell migration. Levels of miR-372 and p62 inversely correlated in human HNSCC tissues. Plasma levels of miR-372 was associated with advanced tumor stage and patient mortality. Both plasma and salivary miR-372 levels were decreased after tumor resection. We conclude that miR-372 decreases p62, thus increasing ROS and motility in HNSCC cells.

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Section: Discussionmentioning

confidence: 99%

miR-372inhibits p62 in head and neck squamous cell carcinomain vitroandin vivo

Yeh¹,

Liu

Wong

et al. 2015

Oncotarget

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“…The inhibition of their activities by a chemical inhibitor or siRNA interference significantly inhibited the migration of dermal fibroblasts induced by bFGF under diabetic conditions, implying that PI3K/Akt, Rac1 and JNK are involved in the regulation of bFGF-promoted dermal fibroblast migration. Several studies showed that Rac1 activation was dependent on PI3K activity and that inhibitors of PI3K/Akt blocked Rac1 activation 22, 31. Moreover, inhibition of the activity of Rac1 reduced JNK activity 32, 33.…”

Section: Discussionmentioning

confidence: 99%

bFGF Promotes the Migration of Human Dermal Fibroblasts under Diabetic Conditions through Reactive Oxygen Species Production via the PI3K/Akt-Rac1- JNK Pathways

Shi¹,

Cheng²,

Ye³

et al. 2015

Int. J. Biol. Sci.

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Fibroblasts play a pivotal role in the process of cutaneous wound repair, whereas their migratory ability under diabetic conditions is markedly reduced. In this study, we investigated the effect of basic fibroblast growth factor (bFGF) on human dermal fibroblast migration in a high-glucose environment. bFGF significantly increased dermal fibroblast migration by increasing the percentage of fibroblasts with a high polarity index and reorganizing F-actin. A significant increase in intracellular reactive oxygen species (ROS) was observed in dermal fibroblasts under diabetic conditions following bFGF treatment. The blockage of bFGF-induced ROS production by either the ROS scavenger N-acetyl-L-cysteine (NAC) or the NADPH oxidase inhibitor diphenylene iodonium chloride (DPI) almost completely neutralized the increased migration rate of dermal fibroblasts promoted by bFGF. Akt, Rac1 and JNK were rapidly activated by bFGF in dermal fibroblasts, and bFGF-induced ROS production and promoted dermal fibroblast migration were significantly attenuated when suppressed respectively. In addition, bFGF-induced increase in ROS production was indispensable for the activation of focal adhesion kinase (FAK) and paxillin. Therefore, our data suggested that bFGF promotes the migration of human dermal fibroblasts under diabetic conditions through increased ROS production via the PI3K/Akt-Rac1-JNK pathways.

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“…Heterodimerisation with non-TAM receptors can occur; interactions with fibromyalgia syndrome-like tyrosine kinase 3 and epidermal growth factor receptor (EGFR) have been previously described in the literature 7 18 19. Furthermore, Axl phosphorylation has also been reported to occur in the presence of reactive oxygen species (ROS) in rat vascular smooth muscle cells 20 21…”

Section: Axl Activation and Signal Transductionmentioning

confidence: 98%

Gene of the month:Axl

et al. 2016

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The interaction between Axl receptor tyrosine kinase and its main ligand Gas6 has been implicated in the progression of a wide number of malignancies. More recently, overexpression of Axl has emerged as a key molecular determinant underlying the development of acquired resistance to targeted anticancer agents. The activation of Axl is overexpression-dependent and controls a number of hallmarks of cancer progression including proliferation, migration, resistance to apoptosis and survival through a complex network of intracellular second messengers. Axl has been noted to influence clinically meaningful end points including metastatic recurrence and survival in the vast majority of tumour types. With Axl inhibitors having gained momentum as novel anticancer therapies, we provide an overview of the biological and clinical relevance of this molecular pathway, outlining the main directions of research.

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Oxidative stress enhances Axl-mediated cell migration through an Akt1/Rac1-dependent mechanism

Cited by 48 publications

References 63 publications

miR-372inhibits p62 in head and neck squamous cell carcinomain vitroandin vivo

miR-372inhibits p62 in head and neck squamous cell carcinomain vitroandin vivo

bFGF Promotes the Migration of Human Dermal Fibroblasts under Diabetic Conditions through Reactive Oxygen Species Production via the PI3K/Akt-Rac1- JNK Pathways

Gene of the month:Axl

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