<scp>MICAL</scp>2 promotes breast cancer cell migration by maintaining epidermal growth factor receptor (<scp>EGFR</scp>) stability and <scp>EGFR</scp>/P38 signalling activation

Wang, Yueyuan; Deng, Wenjie; Zhang, Yujie; Sun, Shixiu; Zhao, Shuo; Chen, Yan; Zhao, Xuyang; Liu, Lei; Du, Jie

doi:10.1111/apha.12920

Cited by 37 publications

(34 citation statements)

References 48 publications

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“…MICAL2 is suggested to be an important regulator of epithelial- to-mesenchymal transition and therefore is a promising target for anti-metastatic therapy 21 . MICAL2 promotes breast cancer cell migration through maintaining epidermal growth factor receptor (EGFR) stability and activating EGFR/P38 signaling 22 . MICAL2-PV is involved in prostate cancer progression, and is suggested to be a novel molecular marker and/or target for treating prostate cancers with a high Gleason score 15 .…”

Section: Introductionmentioning

confidence: 99%

MICAL2 Mediates p53 Ubiquitin Degradation through Oxidating p53 Methionine 40 and 160 and Promotes Colorectal Cancer Malignance

et al. 2018

Theranostics

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Molecule interacting with CasL2 (MICAL2), a microtubule-associated monooxygenase, is highly expressed in various cancers and is involved in cancer pathogenesis, but the mechanisms underlying its regulation in carcinogenesis are unclear. In this study, we aim to clarify the mechanism by which MICAL2 participates in colorectal cancer (CRC) and identify novel markers for predicting prognosis of CRC patients.Methods: The value of MICAL2 in CRC prognosis was determined by immunohistochemical analysis of a CRC biopsy array. A short hairpin RNA target MICAL2 (shMICAL2) was designed to knock down MICAL2 expression and observe MICAL2's function on CRC cell growth. mRNA expression array was used to screen target molecules of MICAL2. HCT116 p53+/+ and HCT116 p53-/- cells were used to confirm whether MICAL2 exerts its oncogenic effect through p53. The in vivo effect of MICAL2 on CRC growth was assessed by subcutaneously injecting MICAL2-knockout CRC cells into the dorsal flank of each mouse. Immunofluorescence was used to observe the effect of MICAL2 on p53 cellular location. Reverse-phase nano ESI-LCMS analysis was used to investigate if MICAL2 mediates p53 oxidation.Results: MICAL2 was found to be highly expressed in CRC tissues, and its expression was associated with CRC carcinogenesis and poor patient outcome. MICAL2-knockdown decreased growth and colony formation of CRC cells, which was linked with cell cycle arrest and apoptosis. MICAL2 physically interacted with p53 and retained p53 in the cytoplasm. MICAL2 shortened the half-life of p53, and ectopic MICAL2 expression decreased p53 protein stability through ubiquitin degradation. MICAL2 was also found to oxidize p53 at methionine 40 and 160, which mediated p53 ubiquitin degradation. MICAL2-promoted CRC growth in vivo was confirmed in nude mice.Conclusion: MICAL2 binds to p53, retains p53 in the cytoplasm and oxidizes it at Met 40 and 160, promotes p53 ubiquitination, and decreases p53 function. MICAL2-reduced p53 promotes CRC development.

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Section: Introductionmentioning

confidence: 99%

MICAL2 Mediates p53 Ubiquitin Degradation through Oxidating p53 Methionine 40 and 160 and Promotes Colorectal Cancer Malignance

et al. 2018

Theranostics

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“…Ectopic expression of MICAL2 in breast cancer cell augments epidermal growth factor receptor (EGFR) expressions, further its mechanism is that MICAL2 triggers a delay in EGFR degradation. MICAL2 may promote cell proliferation and migration 44 .…”

Section: Mical2 Participates In Cell Proliferationmentioning

confidence: 99%

Overexpression of MICAL2, a novel tumor-promoting factor, accelerates tumor progression through regulating cell proliferation and EMT

Cai

Tang

2018

J. Cancer

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Molecule interacting with CasL 2 (MICAL2), a microtubule associated monooxygenase, is involved in cell growth, axon guidance, vesicle trafficking and apoptosis. Recent studies have demonstrated that MICAL2 is highly expressed in tumor and accelerates tumor progression and it is deemed to be a novel tumor-promoting factor. MICAL2 overexpression increases cell proliferation to accelerate tumor growth, and MICAL2 also promotes epithelial-mesenchymal transition (EMT)-related proteins to increase cancer cell metastasis. On mechanism, MICAL2 induces EMT by regulating SRF (serum response factor)/MRTF-A (myocardin related transcription factor A) signaling, Semaphorin/Plexin pathway and inducing ROS (Reactive oxygen species) production. In the present review, we introduced MICAL family, expatiated the structure and functions of MICALs, and summarized the mechanisms of MICAL2 involving tumor progression. The challenges and perspectives for MICAL2 in tumor are also discussed.

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“…However, no significant correlation between wild-type EGFR and the distribution frequency of AURKA SNP rs6024836 for the clinicopathological characteristics of LADC appeared, and the association was nonsignificant when the entire study population with various EGFR phenotypes was evaluated. This phenomenon indicates the relationship of genetic polymorphisms between AURKA and EGFR that may be due to the involvement of cell migration processes from both proteins [ 24 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of Aurora Kinase A Polymorphism and Epithelial Growth Factor Receptor Mutations on the Clinicopathological Characteristics of Lung Adenocarcinoma

Yang

Hsieh

Lee

et al. 2020

IJERPH

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Lung adenocarcinoma (LADC) is the most common subtype of lung cancer worldwide and the epidermal growth factor receptor (EGFR) has a great influence on its clinical course, mainly due to the influence of different phenotypes. The Aurora kinase A (AURKA) would influence the progression of several solid malignancies. However, whether the interaction between EGFR phenotypes and AURKA would influence the clinical characteristics of LADC remains unknown. Herein, this study aimed to explore the effects of single-nucleotide polymorphisms (SNPs) of AURKA and EGFR phenotypes on the clinicopathological characteristics of LADC. Four loci of AURKA SNPs (rs1047972, rs2273535, rs6024836, and rs2064863) were genotyped using TaqMan allelic discrimination in 105 wild-type EGFR individuals and 167 LADC patients with EGFR mutations. After the statistical analysis, patients with LADC who had CT heterozygotes of AURKA rs1047972 had a lower risk of EGFR mutations than patients with wild-type homozygotes. Moreover, female and nonsmoking patients who carried the CT genotype of AURKA rs1047972 had a lower risk of EGFR mutation (p = 0.008 and p = 0.004, respectively). Moreover, in patients with EGFR mutations, AURKA SNP rs6024836 G allele (AG + GG) carriers had a lower risk of developing advanced-stage LADC (stage III or IV; odds ratio = 0.423, 95% confidence interval: 0.203–0.879, p = 0.019) than patients with AA homozygotes. Our results suggested that AURKA rs1047972 variants are significantly associated with EGFR mutations among patients with LADC, particularly in female and nonsmoking patients. AURKA variants may contribute to the pathological development of LADC.

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MICAL2 promotes breast cancer cell migration by maintaining epidermal growth factor receptor (EGFR) stability and EGFR/P38 signalling activation

Abstract: MICAL2 is a major regulator of breast cancer cell migration, maintaining EGFR stability and subsequent EGFR/P38 signalling activation through inhibiting EGFR degradation in a Rac1-dependent manner.

Cited by 37 publications

References 48 publications

MICAL2 Mediates p53 Ubiquitin Degradation through Oxidating p53 Methionine 40 and 160 and Promotes Colorectal Cancer Malignance

MICAL2 Mediates p53 Ubiquitin Degradation through Oxidating p53 Methionine 40 and 160 and Promotes Colorectal Cancer Malignance

Overexpression of MICAL2, a novel tumor-promoting factor, accelerates tumor progression through regulating cell proliferation and EMT

Impact of Aurora Kinase A Polymorphism and Epithelial Growth Factor Receptor Mutations on the Clinicopathological Characteristics of Lung Adenocarcinoma

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