Abstract:
:The correct functioning of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is required for normal skin development and homeostasis. Cellular hyperproliferation induced by dysregulation of EGFR is tightly associated with structural and functional defects of hair follicles, skin lesions, and tumorigenesis. However, a number of questions still remain regarding the mechanism of EGFR activation and signaling. Here, we report that 4.1R, a member of the membrane-cytoskeleton linker FERM family proteins, plays critical roles in EGFR activation and signaling in keratinocytes. We demonstrated that knockout of 4.1R augments the excessive proliferation potential of keratinocytes by immunohistochemical analysis using murine skin samples. 4.1R-/- keratinocytes display enhanced EGFR-mediated Akt/ERK signaling by upregulating EGFR expression and phosphorylation, which can be reversed by either EGFR or MEK phosphorylation inhibitors. Mechanistically, coimmunoprecipitation and immunofluorescent staining results confirmed that 4.1R can impair the activation of EGFR through direct binding to EGFR and reduce the downstream signaling. Taken together, a deficiency of 4.1R would therefore serve to sustain aberrant EGFR-mediated cellular signaling, leading to hyperproliferation. Our findings highlight the role of 4.1R in the regulation of EGFR signaling in keratinocytes and suggest that 4.1R acts as a novel regulator for EGFR activation.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Chen L,Wang T,Ji X,Ding C,Liang T,Liu X,Lu J,Guo X,Kang Q,Ji Zdoi
10.1016/j.yexcr.2019.111648subject
Has Abstractpub_date
2019-11-15 00:00:00pages
111648issue
2eissn
0014-4827issn
1090-2422pii
S0014-4827(19)30515-4journal_volume
384pub_type
杂志文章abstract::The glycolytic enzyme aldolase is concentrated in a domain around stress fibers in living Swiss 3T3 cells, but the mechanism by which aldolase is localized has not been revealed. We have recently identified a molecular binding site for F-actin on aldolase, and we hypothesized that this specific binding interaction, ra...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1997.3811
更新日期:1997-12-15 00:00:00
abstract::In chick embryo fibroblasts, the mRNA for extracellular matrix protein tenascin-C is induced 2-fold by cyclic strain (10%, 0.3 Hz, 6 h). This response is attenuated by inhibiting Rho-dependent kinase (ROCK). The RhoA/ROCK signaling pathway is primarily involved in actin dynamics. Here, we demonstrate its crucial impor...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2005.12.025
更新日期:2006-05-01 00:00:00
abstract::We had identified earlier a germ cell-specific lamin of 60 kDa in rat which is related to somatic lamin B. This polypeptide was shown to be the only major component organizing the lamina structure of round spermatids. In the present study, we find that this 60-kDa polypeptide persists in the testicular and epididymal ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(92)90151-w
更新日期:1992-01-01 00:00:00
abstract::Fibronectin and alpha 1(I) and alpha 2(I) collagen proteins and RNAs are highly expressed during the growth phase of the non-transformed L6 alpha 1 rat myoblasts. When L6 alpha 1 cells from myotubes following transfer to low serum medium, the levels of fibronectin RNA decrease 8-fold, those of both alpha 2(I) transcri...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(86)90497-0
更新日期:1986-10-01 00:00:00
abstract::Tubular epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal tubular interstitial fibrosis (TIF), which subsequently leads to chronic kidney disease (CKD) and eventually, end-stage renal disease (ESRD). We propose that augmenter of liver regeneration (ALR), a member of the newly ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2014.07.001
更新日期:2014-10-01 00:00:00
abstract::Products of the Neuregulin-1 (Nrg-1) gene, along with the ErbB family of receptor tyrosine kinases through which Nrg-1 ligands signal, play a critical role during cardiovascular development. Through studies of genetically manipulated mice, as well as studies in cells isolated from adult hearts, it appears that Nrg-1/E...
journal_title:Experimental cell research
pub_type: 杂志文章,评审
doi:10.1016/j.yexcr.2008.08.015
更新日期:2009-02-15 00:00:00
abstract::Phorbol dibutyrate (PDBu) induced the formation of podosome-like structures together with partial disassembly of actin stress fibers in A7r5 smooth muscle cells. These podosomes contained alpha-actinin, F-actin, and vinculin and exhibit a tubular, column-like structure arising perpendicularly from the bottom of PDBu-t...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.2002.5592
更新日期:2002-10-15 00:00:00
abstract::Advanced stage neuroblastomas (NB) exhibit a tissue inhibitor of metalloproteinase (TIMP)-2/matrix metalloproteinase (MMP) imbalance, considered a prerequisite for MMP involvement in tumor progression in vivo. Human SH-SY5Y NB cells exhibit a similar TIMP-2/MMP imbalance that promotes in vitro invasive behavior that i...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/s0014-4827(03)00072-7
更新日期:2003-06-10 00:00:00
abstract::We have earlier shown that mouse pancreatic acinar cells produce hydrogen sulfide (H(2)S), which plays a key role in the pathogenesis of acute pancreatitis (AP). H(2)S-dependent induction of inflammation is mediated by the activation of transcription factor NF-kappaB. We now provide evidence that activation of Src fam...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2010.02.044
更新日期:2010-05-15 00:00:00
abstract::LIM domain proteins are important regulators of the growth, determination, and differentiation of cells. In this report, FHL3 (human four-and-a-half LIM-only protein 3) is shown to interact with human phosphatase CDC25B, a cell cycle regulator involved in the control of G2/M. We found that this interaction was specifi...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/s0014-4827(03)00018-1
更新日期:2003-04-15 00:00:00
abstract::Breast cancer and prostate cancer are the most common malignant tumors in female and men, respectively. Furthermore, lung cancer is the leading cause of cancer deaths worldwide. It is an emergency to develop a powerful strategy to treat these threatening cancers more effectively, because of low efficacy and high rates...
journal_title:Experimental cell research
pub_type: 杂志文章,评审
doi:10.1016/j.yexcr.2018.03.023
更新日期:2018-06-01 00:00:00
abstract::Murine embryonal carcinoma F9 cells can be induced to differentiate by 2-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC). The differentiated phenotype is similar to that of retinoic acid (RA)-treated F9 cells. In contrast to F9 cells the differentiated cells secrete plasminog...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(85)90276-9
更新日期:1985-01-01 00:00:00
abstract::Liver cells of new-born rats, which were found to be able to form spheroidal aggregates when cultured on a nonadherent plastic substratum, were studied under various conditions of culture, mainly by adding different nutrients and growth factors to the culture medium. Analysis of hepatocyte-specific functions was carri...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(90)90260-h
更新日期:1990-07-01 00:00:00
abstract::We have reported that PAP-1, a product of a causative gene for autosomal retinitis pigmentosa, plays a role in splicing. In this study, CIR, a protein originally identified as a CBF1-interacting protein and reported to act as a transcriptional corepressor, was identified as a PAP-1 binding protein and its function as ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2004.10.012
更新日期:2005-02-15 00:00:00
abstract::We have previously shown that following psoralen photoactivation (PUVA treatment) human dermal fibroblasts undergo long-term growth arrest as well as morphological and functional changes reminiscent of cellular senescence [ 1 ]. In the absence of molecular data on what constitutes normal senescence, it has been diffic...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.2002.5476
更新日期:2002-04-01 00:00:00
abstract::A monoclonal antibody raised against microtubule-associated protein-1 (MAP-1) binds to nuclei of normal human fibroblasts, its binding site being detected as intranuclear immunofluorescent dots. The percentage of cells showing these dots increased with insulin, hydrocortisone, epidermal growth factor (EGF), and transf...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(85)90480-x
更新日期:1985-06-01 00:00:00
abstract::PHOX2B and its paralogue gene PHOX2A are two homeodomain proteins in the network regulating the development of autonomic ganglia that have been associated with the pathogenesis of neuroblastoma (NB), because of their over-expression in different NB cell lines and tumour samples. We used the SK-N-BE(2)C cell line to sh...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2016.02.014
更新日期:2016-03-01 00:00:00
abstract::Template-activating factors I (TAF-I) alpha and beta have been identified as chromatin remodeling factors from human HeLa cells. TAF-I beta corresponds to the protein encoded by the set gene, which was found in an acute undifferentiated leukemia as a fusion version with the can gene via chromosomal translocation. To d...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1997.3930
更新日期:1998-05-01 00:00:00
abstract::Adriamycin, an anticancer agent acting on topoisomerase II, promotes the arrest of cell division and neurite extension in a "neurite-minus" murine neuroblastoma cell line, N1A-103. This morphological differentiation is accompanied by a blockade in the S phase of the cell cycle, modification of the amount of peripherin...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(92)90041-6
更新日期:1992-11-01 00:00:00
abstract::Although periodontal diseases are initiated by bacteria that colonize the tooth surface and gingival sulcus, the host response is believed to play an essential role in the breakdown of connective tissue and bone. Mitochondrial reactive oxygen species (mtROS) have been proposed to regulate the activation of the inflamm...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2016.08.007
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abstract::Alpha-Smooth muscle actin is one of the molecular markers for a phenotype of vascular smooth muscle cells, because the actin is a major isoform expressed in vascular smooth muscle cells and its expression is upregulated during differentiation. Here, we first demonstrate that the phenotype-dependent expression of this ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1998.4339
更新日期:1999-02-25 00:00:00
abstract::We have studied the use of electrofusion to obtain hybridomas producing antigen-specific antibodies after immunization of murine lymphocytes in vitro. Under optimal conditions fusion frequencies of the order of magnitude of 10(-3) were obtained, which is approximately 80-fold higher than the mean value obtained with f...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(89)90405-9
更新日期:1989-08-01 00:00:00
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journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
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doi:10.1016/j.yexcr.2003.12.010
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abstract::The poor outcome of hepatocellular carcinoma (HCC) is mainly due to the development of fast growth, invasion and metastasis. The role of TET2 has been implicated in some cancer types, but its role and mechanisms in HCC remains elusive. In this study, our findings indicated that TET2 expression frequently increased in ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2018.01.011
更新日期:2018-02-15 00:00:00
abstract::Previous studies have shown that calpains are autolytically cleaved during the disease process of mdx dystrophy, a mouse model for Duchenne muscular dystrophy, indicating that calpains may be activated and play a role in proteolysis that occurs in muscular dystrophy (J. Biol. Chem. 270(18), 10909-10914, 1995). In the ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1996.0227
更新日期:1996-08-01 00:00:00
abstract::The migration and proliferation of vascular smooth muscle cells (vSMCs) are critical events in neointima formation during atherosclerosis and restenosis. The transcription factor nuclear factor of activated T-cells-isoform c1 (NFATc1) is regulated by atherogenic cytokines, and has been implicated in the migratory and ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2008.07.010
更新日期:2008-10-01 00:00:00
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1995.1080
更新日期:1995-04-01 00:00:00
abstract::Pair formation in the hypotrichous ciliate Euplotes octocarinatus is a poorly understood phenomenon. In order to obtain information about the molecules involved in this process, we compared ciliary and cell body-associated glycoconjugates of non-mating-competent, mating-competent, and conjugating cells. Detection of g...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1995.1114
更新日期:1995-04-01 00:00:00
abstract::Galectin-3, a beta-galactoside-binding protein, has been shown to be involved in multiple biological processes through interaction with its complementary glycoconjugates. Here we provide the first evidence of galectin-3 as a mitogen. Incubation of quiescent cultures of normal human lung fibroblast IMR-90 cells with re...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1998.4253
更新日期:1998-12-15 00:00:00