Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells

Alsharif, Sarah; Sharma, Pooja; Bursch, Karina; Milliken, Rachel; Lam, Van; Fallatah, Arwa; Phan, Thuc; Collins, Meagan; Dohlman, Priya; Tiufekchiev, Sarah; Nehmetallah, George; Raub, Christopher B.; Chung, Byung Min

doi:10.1080/19336918.2020.1868694

Cited by 16 publications

(8 citation statements)

References 71 publications

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“… Li et al (2018) pointed out that KRT80 is an independent prognostic biomarker for CRC and promotes CRC migration and invasion by activating the AKT pathway and interacting with PRKDC. Alsharif et al (2021) suggested that KRT19 was highly expressed in breast cancer and could stabilize the E-cadherin complex on the cell membrane, maintain cell–cell adhesion, and provide growth and survival advantages for tumor cells. The GO term and KEGG pathway analysis of top 200 co-expressed genes positively associated with SLC2A1 expression indicated that these genes were mainly correlated to epidermis development, cell–cell junction, and cadherin binding.…”

Section: Discussionmentioning

confidence: 99%

SLC2A1 is a Diagnostic Biomarker Involved in Immune Infiltration of Colorectal Cancer and Associated With m6A Modification and ceRNA

Liu

Yang

Zeng

et al. 2022

Front. Cell Dev. Biol.

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Background: Overexpression of solute carrier family 2 member 1 (SLC2A1) promotes glycolysis and proliferation and migration of various tumors. However, there are few comprehensive studies on SLC2A1 in colorectal cancer (CRC).Methods: Oncomine, The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases were used to analyze the expression of SLC2A1 in pan-cancer and CRC and analyzed the correlation between SLC2A1 expression and clinical characteristics of TCGA CRC samples. The expression level of SLC2A1 in CRC was certified by cell experiments and immunohistochemical staining analysis. The Genome Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses of SLC2A1 relative genes were completed by bioinformatics analysis. The correlation between SLC2A1 expression level and CRC immune infiltration cell was analyzed by Tumor IMmune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and TCGA database. The correlation between SLC2A1 expression level and ferroptosis and m6A modification of CRC was analyzed by utilizing TCGA and GEO cohort. Finally, the possible competing endogenous RNA (ceRNA) networks involved in SLC2A1 in CRC are predicted and constructed through various databases.Results: SLC2A1 is highly expressed not only in CRC but also in many other tumors. ROC curve indicated that SLC2A1 had high predictive accuracy for the outcomes of tumor. The SLC2A1 expression in CRC was closely correlated with tumor stage and progression free interval (PFI). GO, KEGG, and GSEA analysis indicated that SLC2A1 relative genes were involved in multiple biological functions. The analysis of TIMER, GEPIA, and TCGA database indicated that the SLC2A1 mRNA expression was mainly positively associated with neutrophils. By the analysis of the TCGA and GEO cohort, we identified that the expression of SLC2A1 is closely associated to an m6A modification relative gene Insulin Like Growth Factor 2 MRNA Binding Protein 3 (IGF2BP3) and a ferroptosis relative gene Glutathione Peroxidase 4 (GPX4).Conclusion: SLC2A1 can be used as a biomarker of CRC, which is associated to immune infiltration, m6A modification, ferroptosis, and ceRNA regulatory network of CRC.

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Section: Discussionmentioning

confidence: 99%

SLC2A1 is a Diagnostic Biomarker Involved in Immune Infiltration of Colorectal Cancer and Associated With m6A Modification and ceRNA

Liu

Yang

Zeng

et al. 2022

Front. Cell Dev. Biol.

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“…There were no observable differences in adhesion under shear stress conditions on surfaces coated with membrane‐bound ICAM1 ( mb ‐ICAM‐1), immobilized ICAM1 ( im ‐ICAM‐1), and fibronectin (Figure S5B–D , Supporting Information). Since cytoplasmic keratins have been reported to localize proteins to either the cell surface or cytoplasm, [ 4 , 5 , 32 ] we tested whether the collagen binding protein integrin β1 localization was affected by tKRT81 expression to determine if this was the mechanism behind the observed adhesion phenotype. However, flow cytometry analysis in LuM1 and MDA‐MB‐361 control, tKRT81 knockdown, and rescue cells showed no difference in cell surface expression of integrin β1 (Figure S5E,F , Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

“…[ 4 ] KRT19 has been shown to help localize E‐cadherin to the cell membrane, facilitating cell‐cell adhesion. [ 5 ] KRT14 is perhaps the most well‐characterized keratin in the context of cancer and has been shown to be concentrated in the leading edge of collectively invading breast cancer cells [ 6 , 7 ] and to facilitate the invasion of ovarian cancer cells. [ 8 ] Keratin expression has also been linked to poor patient outcomes.…”

Section: Introductionmentioning

confidence: 99%

Ectopic Expression of a Truncated Isoform of Hair Keratin 81 in Breast Cancer Alters Biophysical Characteristics to Promote Metastatic Propensity

Kang,

Moriarty,

Wang

et al. 2023

Advanced Science

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Keratins are an integral part of cell structure and function. Here, it is shown that ectopic expression of a truncated isoform of keratin 81 (tKRT81) in breast cancer is upregulated in metastatic lesions compared to primary tumors and patient‐derived circulating tumor cells, and is associated with more aggressive subtypes. tKRT81 physically interacts with keratin 18 (KRT18) and leads to changes in the cytosolic keratin intermediate filament network and desmosomal plaque formation. These structural changes are associated with a softer, more elastically deformable cancer cell with enhanced adhesion and clustering ability leading to greater in vivo lung metastatic burden. This work describes a novel biomechanical mechanism by which tKRT81 promotes metastasis, highlighting the importance of the biophysical characteristics of tumor cells.

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“…Keratin filaments regulate the subcellular localization of several proteins [ 25 , 27 – 29 ], and we hypothesized that K19 may influence the localization of the typically predominantly nuclear HNRNPK. Therefore, we examined the cytoplasmic and nuclear levels of HNRNPK in parental and KRT19 KO cells.…”

Section: Resultsmentioning

confidence: 99%

Keratin 19 binds and regulates cytoplasmic HNRNPK mRNA targets in triple-negative breast cancer

Fallatah,

Anastasakis,

Manzourolajdad

et al. 2023

BMC Mol and Cell Biol

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Background Heterogeneous nuclear ribonucleoprotein K (HNRNPK) regulates pre-mRNA processing and long non-coding RNA localization in the nucleus. It was previously shown that shuttling of HNRNPK to the cytoplasm promotes cell proliferation and cancer metastasis. However, the mechanism of HNRNPK cytoplasmic localization, its cytoplasmic RNA ligands, and impact on post-transcriptional gene regulation remain uncharacterized. Results Here we show that the intermediate filament protein Keratin 19 (K19) directly interacts with HNRNPK and sequesters it in the cytoplasm. Correspondingly, in K19 knockout breast cancer cells, HNRNPK does not localize in the cytoplasm, resulting in reduced cell proliferation. We comprehensively mapped HNRNPK binding sites on mRNAs and showed that, in the cytoplasm, K19-mediated HNRNPK-retention increases the abundance of target mRNAs bound to the 3’ untranslated region (3’UTR) at the expected cytidine-rich (C-rich) sequence elements. Furthermore, these mRNAs protected by HNRNPK in the cytoplasm are typically involved in cancer progression and include the p53 signaling pathway that is dysregulated upon HNRNPK knockdown (HNRNPK KD) or K19 knockout (KRT19 KO). Conclusions This study identifies how a cytoskeletal protein can directly regulate gene expression by controlling the subcellular localization of RNA-binding proteins to support pathways involved in cancer progression.

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Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells

Cited by 16 publications

References 71 publications

SLC2A1 is a Diagnostic Biomarker Involved in Immune Infiltration of Colorectal Cancer and Associated With m6A Modification and ceRNA

SLC2A1 is a Diagnostic Biomarker Involved in Immune Infiltration of Colorectal Cancer and Associated With m6A Modification and ceRNA

Ectopic Expression of a Truncated Isoform of Hair Keratin 81 in Breast Cancer Alters Biophysical Characteristics to Promote Metastatic Propensity

Keratin 19 binds and regulates cytoplasmic HNRNPK mRNA targets in triple-negative breast cancer

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