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    ACTN4 actinin alpha 4 [ Homo sapiens (human) ]

    Gene ID: 81, updated on 12-Oct-2019

    GeneRIFs: Gene References Into Functions

    GeneRIFPubMed TitleDate
    Serum ACTN4 level was obviously upregulated in patients with BC compared with healthy controls (P<0.05). High ACTN4 expression was significantly associated with clinical stage (P=0.000), tumor grade (P=0.004), and lymph node status (P=0.024).

    Actinin-4 as a Diagnostic Biomarker in Serum of Breast Cancer Patients.
    Fang C, Li JJ, Deng T, Li BH, Geng PL, Zeng XT., Free PMC Article

    Overexpression of ACTN4 has positive effect on cells with inactive RelA/p65 but severely enhances its inhibitory effect, possibly via induction of apoptosis.

    Co-expression of RelA/p65 and ACTN4 induces apoptosis in non-small lung carcinoma cells.
    Lomert E, Turoverova L, Kriger D, Aksenov ND, Nikotina AD, Petukhov A, Mittenberg AG, Panyushev NV, Khotin M, Volkov K, Barlev NA, Tentler D., Free PMC Article

    Here, the authors identified an important EGFR-interacting protein, alpha-actinin-4 (ACTN4), which is involved in maintaining and regulating the actin cytoskeleton. They observed that transactivated-EGFR competitively recruited ACTN4 from intracellular F-actin fibers to disrupt the cytoskeleton, thus facilitating bacterial invasion of brain microvascular endothelial cells.

    Transactivated Epidermal Growth Factor Receptor Recruitment of α-actinin-4 From F-actin Contributes to Invasion of Brain Microvascular Endothelial Cells by Meningitic <i>Escherichia coli</i>.
    Fu J, Li L, Yang X, Yang R, Amjad N, Liu L, Tan C, Chen H, Wang X., Free PMC Article

    Study reported that NHERF1 reduced the stability and expression levels of ACTN4, and led to inhibition of the assembly of actin filaments in cervical cancer cells.

    HPV16 E6 promotes cervical cancer cell migration and invasion by downregulation of NHERF1.
    Wang Q, Song R, Zhao C, Liu H, Yang Y, Gu S, Feng D, He J.

    Through driving a feedforward signaling axis of ACTN4-RIPK1-NF-kappaB.

    ACTN4 regulates the stability of RIPK1 in melanoma.
    Zhang YY, Tabataba H, Liu XY, Wang JY, Yan XG, Farrelly M, Jiang CC, Guo ST, Liu T, Kao HY, Thorne RF, Zhang XD, Jin L.

    we summarize current knowledge regarding therapeutic strategies for locally advanced pancreatic cancer and discuss the potential development of personalized medicine using ACTN4 measurement for patients with locally advanced pancreatic cancer--{REVIEW}

    Measurement of copy number of ACTN4 to optimize the therapeutic strategy for locally advanced pancreatic cancer.
    Shoji H, Miura N, Ueno H, Honda K.

    Actinin-4 directly binds to the cytosolic tail of CD147 and governs the assembly of CD147-beta2-adrenergic receptor complexes in highly ordered clusters at bacterial adhesion sites.Actinin-4 is recruited to bacterial adhesion sites.

    Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β<sub>2</sub>-adrenoceptor clusters assembled by alpha-actinin-4.
    Maïssa N, Covarelli V, Janel S, Durel B, Simpson N, Bernard SC, Pardo-Lopez L, Bouzinba-Ségard H, Faure C, Scott MGH, Coureuil M, Morand PC, Lafont F, Nassif X, Marullo S, Bourdoulous S., Free PMC Article

    significantly upregulated in the cervical mucus of women with preterm labor with microbial invasion of the amniotic cavity

    Cervical Alpha-Actinin-4 Is Upregulated in Women with Threatened Preterm Labor and Microbial Invasion of the Amniotic Cavity.
    Cobo T, Palacio M, Grande M, Sánchez-García AB, Estanyol JM, López M, Bosch J, Martí C, Gratacós E.

    Data suggest that TYRO3-mediated phosphorylation of ACTN4 is involved in invasiveness of melanoma cells; TYRO3-mediated phosphorylation of ACTN4 requires FAK activation at tyrosine 397. (TYRO3 = TYRO3 protein tyrosine kinase; ACTN4 = actinin alpha 4; FAK = focal adhesion kinase isoform FAK1)

    Tyro3-mediated phosphorylation of ACTN4 at tyrosines is FAK-dependent and decreases susceptibility to cleavage by m-Calpain.
    Shao H, Wang A, Lauffenburger D, Wells A., Free PMC Article

    ACTN4 knockdown resulted in the blockage of malignant cell proliferation, colony formation, and ameliorated metastasis potency. ACTN4-positive CSCs exhibited a higher ESA(+) proportion, increased mammosphere-formation ability, and enhanced in vivo tumorigenesis ability.

    Direct inhibition of ACTN4 by ellagic acid limits breast cancer metastasis via regulation of β-catenin stabilization in cancer stem cells.
    Wang N, Wang Q, Tang H, Zhang F, Zheng Y, Wang S, Zhang J, Wang Z, Xie X., Free PMC Article

    These results demonstrate that both actinin-1 and actinin-4 participate in the assembly of F-actin at invadopodia. Additionally, actinin-4 may have a selective advantage in accelerating invadopodia-mediated invasion of carcinoma cells.

    Actinin-1 and actinin-4 play essential but distinct roles in invadopodia formation by carcinoma cells.
    Yamaguchi H, Ito Y, Miura N, Nagamura Y, Nakabo A, Fukami K, Honda K, Sakai R.

    Gene amplification of ACTN4 was a significant independent risk factor for death in patients with stage I/II oral tongue cancer (hazard ratio 6.08, 95% confidence interval 1.66-22.27). Gene amplification of ACTN4 is a potential prognostic biomarker for overall survival in oral tongue cancer.

    Prognostic significance of gene amplification of ACTN4 in stage I and II oral tongue cancer.
    Kakuya T, Mori T, Yoshimoto S, Watabe Y, Miura N, Shoji H, Onidani K, Shibahara T, Honda K.

    ACTN4 knockdown near-completely abrogates both radioresistance and epithelial-mesenchymal transition-associated changes in breast cancer cells.

    α-Actinin-4 confers radioresistance coupled invasiveness in breast cancer cells through AKT pathway.
    Desai S, Barai A, Bukhari AB, De A, Sen S.

    Fascin and alpha-actinin intrinsically segregate to discrete bundled domains that are specifically recognized by other actin-binding proteins.

    Fascin- and α-Actinin-Bundled Networks Contain Intrinsic Structural Features that Drive Protein Sorting.
    Winkelman JD, Suarez C, Hocky GM, Harker AJ, Morganthaler AN, Christensen JR, Voth GA, Bartles JR, Kovar DR., Free PMC Article

    Suggest that ACTN4 as a potential predictive biomarker for efficacy of adjuvant chemotherapy in stage-IB/II patients with non-small cell lung cancer, by reflecting the metastatic potential of tumor cells.

    Efficacy of adjuvant chemotherapy for non-small cell lung cancer assessed by metastatic potential associated with ACTN4.
    Miura N, Kamita M, Kakuya T, Fujiwara Y, Tsuta K, Shiraishi H, Takeshita F, Ochiya T, Shoji H, Huang W, Ohe Y, Yamada T, Honda K., Free PMC Article

    High ACTN4 expression is associated with Lung Squamous Cell Carcinoma.

    A Two-Gene Prognostic Classifier for Early-Stage Lung Squamous Cell Carcinoma in Multiple Large-Scale and Geographically Diverse Cohorts.
    Noro R, Ishigame T, Walsh N, Shiraishi K, Robles AI, Ryan BM, Schetter AJ, Bowman ED, Welsh JA, Seike M, Gemma A, Skaug V, Mollerup S, Haugen A, Yokota J, Kohno T, Harris CC., Free PMC Article

    Our findings indicate that ACTN4 promotes EMT and tumorigenesis by regulating Snail expression and the Akt pathway in cervical cancer. We propose a novel mechanism for EMT and tumorigenesis in cervical cancer.

    α-Actinin-4 induces the epithelial-to-mesenchymal transition and tumorigenesis via regulation of Snail expression and β-catenin stabilization in cervical cancer.
    An HT, Yoo S, Ko J.

    Study found a functional Validation of an Alpha-Actinin-4 Mutation as a Potential Cause of an Aggressive Presentation of Adolescent Focal Segmental Glomerulosclerosis.

    Functional Validation of an Alpha-Actinin-4 Mutation as a Potential Cause of an Aggressive Presentation of Adolescent Focal Segmental Glomerulosclerosis: Implications for Genetic Testing.
    Feng D, Steinke JM, Krishnan R, Birrane G, Pollak MR., Free PMC Article

    SERPINE1, ANGPLT4, CCL20, and SAA1 as well as the NF-kappaB (p65) binding sites on GR-transrepressed promoters such as IL-1beta, IL-6, and IL-8 Taken together, our data establish ACTN4 as a transcriptional co-regulator that modulates both dexamethasone-transactivated and -transrepressed genes in podocytes.

    α Actinin 4 (ACTN4) Regulates Glucocorticoid Receptor-mediated Transactivation and Transrepression in Podocytes.
    Zhao X, Khurana S, Charkraborty S, Tian Y, Sedor JR, Bruggman LA, Kao HY., Free PMC Article

    Here, we report the identification of a novel, disease-causing ACTN4 mutation (p.G195D, de novo) in a sporadic case of childhood FSGS using next generation sequencing.

    Three-layered proteomic characterization of a novel ACTN4 mutation unravels its pathogenic potential in FSGS.
    Bartram MP, Habbig S, Pahmeyer C, Höhne M, Weber LT, Thiele H, Altmüller J, Kottoor N, Wenzel A, Krueger M, Schermer B, Benzing T, Rinschen MM, Beck BB.

    the calmodulin domain of human alpha-actinin-4 binding to the linker region was important for regulating the distance between actin and actin-binding domain.

    Dynamic Regulation of α-Actinin's Calponin Homology Domains on F-Actin.
    Shams H, Golji J, Garakani K, Mofrad MR., Free PMC Article

    This study identified alpha-actinin-4 as a novel NHERF1 interaction partner and provided new insights into the regulatory mechanism of the actin cytoskeleton by NHERF1.

    NHERF1 regulates actin cytoskeleton organization through modulation of α-actinin-4 stability.
    Sun L, Zheng J, Wang Q, Song R, Liu H, Meng R, Tao T, Si Y, Jiang W, He J.

    Selective regulation of NF-kappaB gene targets may indicate involvement of ACTN4 in determining the specificity of cell response to NF-kappaB activation in cells of different types. (Review)

    Panyushev NV, Tentler DG.

    ZYX defective binding to ACTN4, which occupies focal adhesions instead of ACTN1, induces the formation of immature focal adhesions, resulting in the enhancement of cell motility and invasion.

    α-Actinin-4 enhances colorectal cancer cell invasion by suppressing focal adhesion maturation.
    Fukumoto M, Kurisu S, Yamada T, Takenawa T., Free PMC Article

    The contribution of ACTN4 to the process of lung cancer metastasis to the brain could be mainly through regulation of actin cytoskeleton reorganization, cell motility, and focal adhesion.

    ACTN4 and the pathways associated with cell motility and adhesion contribute to the process of lung cancer metastasis to the brain.
    Gao Y, Li G, Sun L, He Y, Li X, Sun Z, Wang J, Jiang Y, Shi J., Free PMC Article

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