Silencing of MICAL-L2 suppresses malignancy of ovarian cancer by inducing mesenchymal–epithelial transition

Zhu, Linyan; Zhang, Wenming; Yang, Xiaomei; Cui, Lining; Li, Jun; Zhang, Yanli; Wang, Yahui; Ao, Junping; Ma, Mingze; Lu, Huan; Ren, Yuan; Xu, Shaohua; Yang, Guangdong; Song, Weiwei; Wang, Jing-Hao; Zhang, Xiaodan; Zhang, Rong; Zhang, Zhigang

doi:10.1016/j.canlet.2015.04.002

Cited by 36 publications

(44 citation statements)

References 38 publications

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“…MICAL-dependent depolymerization of actin has been involved in processes as diverse as axonal guidance 97,105 , phagocytosis by macrophages 112 , vesicle trafficking 102 , epithelial to mesenchymal transition (EMT) 115–117 , and cancer invasion and metastasis 115,116,118,119 . Three paralogous genes were identified in mammals, named MICAL1–3 97 , with different distribution patterns in embryonic and adult tissues 95,109,120 .…”

Section: Micalmentioning

confidence: 99%

“…Binding of MICAL-L2 to F-actin is inhibited by its own CTD 134 , a mechanism conserved with MICAL1 (see below) 109,140 . MICAL-L2 was also identified as a key element in promoting cell migration in ovarian cancer cell lines 118 . Overall, besides the absence of the active FMO domain in MICAL-L proteins, they can still regulate actin dynamics and, taking into account that they share interaction domains and regulatory sites, a direct interaction with MICAL proteins cannot be excluded and may be an interesting avenue for future studies.…”

Section: Micalmentioning

confidence: 99%

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Regulated methionine oxidation by monooxygenases

Manta

Gladyshev

2017

Free Radical Biology and Medicine

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Protein function can be regulated via post-translational modifications by numerous enzymatic and non-enzymatic mechanisms, including oxidation of cysteine and methionine residues. Redox-dependent regulatory mechanisms have been identified for nearly every cellular process, but the major paradigm has been that cellular components are oxidized (damaged) by reactive oxygen species (ROS) in a relatively unspecific way, and then reduced (repaired) by designated reductases. While this scheme may work with cysteine, it cannot be ascribed to other residues, such as methionine, whose reaction with ROS is too slow to be biologically relevant. However, methionine is clearly oxidized in vivo and enzymes for its stereoselective reduction are present in all three domains of life. Here, we revisit the chemistry and biology of methionine oxidation, with emphasis on its generation by enzymes from the monooxygenase family. Particular attention is placed on MICALs, a recently discovered family of proteins that harbor an unusual flavin-monooxygenase domain with an NADPH-dependent methionine sulfoxidase activity. Based on the structural and kinetic information we provide a rational framework to explain MICAL mechanism, inhibition, and regulation. Methionine residues that are targeted by MICALs are reduced back by methionine sulfoxide reductases, suggesting that reversible methionine oxidation may be a general mechanism analogous to the regulation by phosphorylation by kinases/phosphatases. The identification of new enzymes that catalyze the oxidation of methionine will open a new area of research at the forefront of redox signaling.

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Section: Micalmentioning

confidence: 99%

Section: Micalmentioning

confidence: 99%

Regulated methionine oxidation by monooxygenases

Manta

Gladyshev

2017

Free Radical Biology and Medicine

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“…FAD domain contains flavin mono‐oxygenase activity and is responsible for majority of MICAL1's function 9. Recently, overexpression of MICAL2 and MICAL‐L2, the other members of MICAL family, has been confirmed to be related to multiple invasive phenotype of cancer cells such as increased motility, proliferation, as well as inducing epithelial‐to‐mesenchymal transition (EMT) 10, 11. Domain architecture of MICAL1 is closely related to Drosophila MICAL4; however, to date, only a few reports characterizing the functions of MICAL1 in human cancer progression have been published.…”

Section: Introductionmentioning

confidence: 99%

MICAL1 facilitates breast cancer cell proliferation via ROS‐sensitive ERK/cyclin D pathway

Deng

Wang

Zhao

et al. 2018

J Cellular Molecular Medi

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Molecule interacting with CasL 1 (MICAL1) is a multidomain flavoprotein mono‐oxygenase that strongly involves in cytoskeleton dynamics and cell oxidoreduction metabolism. Recently, results from our laboratory have shown that MICAL1 modulates reactive oxygen species (ROS) production, and the latter then activates phosphatidyl inositol 3‐kinase (PI3K)/protein kinase B (Akt) signalling pathway which regulates breast cancer cell invasion. Herein, we performed this study to assess the involvement of MICAL1 in breast cancer cell proliferation and to explore the potential molecular mechanism. We noticed that depletion of MICAL1 markedly reduced cell proliferation in breast cancer cell line MCF‐7 and T47D. This effect of MICAL1 on proliferation was independent of wnt/β‐catenin and NF‐κB pathways. Interestingly, depletion of MICAL1 significantly inhibited ROS production, decreased p‐ERK expression and unfavourable for proliferative phenotype of breast cancer cells. Likewise, MICAL1 overexpression increased p‐ERK level as well as p‐ERK nucleus translocation. Moreover, we investigated the effect of MICAL1 on cell cycle‐related proteins. MICAL1 positively regulated CDK4 and cyclin D expression, but not CDK2, CDK6, cyclin A and cyclin E. In addition, more expression of CDK4 and cyclin D by MICAL1 overexpression was blocked by PI3K/Akt inhibitor LY294002. LY294002 treatment also attenuated the increase in the p‐ERK level in MICAL1‐overexpressed breast cancer cells. Together, our results suggest that MICAL1 exhibits its effect on proliferation via maintaining cyclin D expression through ROS‐sensitive PI3K/Akt/ERK signalling in breast cancer cells.

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“…lated in ovarian cancer tissue, and knockdown of MICAL-L2 suppresses the proliferation, migration, and invasive capacity of ovarian cancer cells in culture (74). One actin-bundling protein that is recruited by activated MICAL-L2 is filamin.…”

Section: Cell Migration and Scatteringmentioning

confidence: 99%

Regulation of Cancer Cell Behavior by the Small GTPase Rab13

Ioannou

McPherson

2016

Journal of Biological Chemistry

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The members of the Rab family of GTPases are master regulators of cellular membrane trafficking. With ϳ70 members in humans, Rabs have been implicated in all steps of membrane trafficking ranging from vesicle formation and transport to vesicle docking/tethering and fusion. Vesicle trafficking controls the localization and levels of a myriad of proteins, thus regulating cellular functions including proliferation, metabolism, cellcell adhesion, and cell migration. It is therefore not surprising that impairment of Rab pathways is associated with diseases including cancer. In this review, we highlight evidence supporting the role of Rab13 as a potent driver of cancer progression.The members of the Rab (Ras-related in brain) family of proteins are master regulators of vesicle trafficking. They are evolutionarily conserved with ϳ70 members in humans, and each Rab is localized predominantly to a specific intracellular organelle or vesicle (1). Rabs have been implicated in every step of vesicle trafficking including the formation of cargo-laden membrane vesicles and tubules, transport of these carriers on the cytoskeleton, tethering and docking of the carriers at the target membrane, and finally membrane fusion and delivery of cargo. Not surprisingly, functional impairment of Rab pathways is associated with diseases including immunodeficiencies, neurological disorders, and cancer (2). One such Rab, Rab13, controls cellular functions that are often altered in cancer, and Rab13 is now recognized as an important driver of cancer progression. Here, we discuss the importance of Rab13 in the physiology of cancer with a focus on Rab13 trafficking pathways contributing to tumorigenicity. The Biology of Rab13As for all small GTPases, Rab13 cycles between an active, GTP-bound state and an inactive, GDP-bound state. Activation of Rab13 is mediated by DENND2B and DENND1C/connecdenn 3, guanine nucleotide exchange factors (GEFs) 2 that interact with GDP-bound Rab13 and facilitate the exchange of GDP for GTP (3-5). These proteins each bear a differentially expressed in normal and neoplastic cells (DENN) domain, an evolutionarily ancient protein module that encodes GEF activity for a large number of Rab GTPases (6 -8). Rab13 is inactivated by the GTPase-activating protein (GAP) Akt substrate 160 (AS160)/TBC1D4, which enhances the ability of Rab13 to hydrolyze GTP (3-5). In its active form, Rab13 binds to several effectors including MICAL-L1, MICAL-L2, and PKA (9, 10). Rab13, which is ubiquitously expressed, is thought to have diverged from its closest homologue Rab8, early in the vertebrate lineage (11). Similar to Rab8, Rab13 has been implicated in both biosynthetic and endosomal recycling pathways. Rab13 is found at the trans-Golgi network, on recycling endosomes, on late endosomes, and at the plasma membrane (12-14). Disruption of Rab13 function inhibits the delivery of cargo that reaches the plasma membrane via endosomes from either the biosynthetic or the endocytic recycling pathways. Thus, Rab13 is thought to control membrane t...

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Silencing of MICAL-L2 suppresses malignancy of ovarian cancer by inducing mesenchymal–epithelial transition

Cited by 36 publications

References 38 publications

Regulated methionine oxidation by monooxygenases

Regulated methionine oxidation by monooxygenases

MICAL1 facilitates breast cancer cell proliferation via ROS‐sensitive ERK/cyclin D pathway

Regulation of Cancer Cell Behavior by the Small GTPase Rab13

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