Dataset Information

α-catenin interacts with YAP/FoxM1/TEAD-induced CEP55 and fosters liver cancer cell migration

ABSTRACT: Aberrant expression of adherens junction (AJ) proteins is frequently observed in human cancers. However, how these factors contribute to tumorigenesis is poorly understood and for some factors such as α‐catenin contradicting data has been described. Systematic analysis of TCGA expression data derived from 23 human tumor types revealed that α‐catenin was significantly reduced in some malignancies (e.g., colon adenocarcinoma), while elevated α‐catenin expression in other entities was associated with poor clinical outcome (e.g., hepatocellular carcinoma; HCC). In HCC cells, α‐catenin was detectable at the membrane as well as cytoplasm where it supported tumor cell proliferation and migration. Additionally, in vivo experiments illustrated moderate oncogenic potential of α‐catenin. To identify functionally relevant binding partners of α‐catenin, BioID combined with mass spectrometry was performed. This led to the identification of cytokinesis regulator centrosomal protein 55 (CEP55) as novel α‐catenin interacting protein in the cytoplasm that was stabilized by α‐catenin. Interestingly, CEP55 was highly expressed in human HCC tissues and its overexpression was transcriptionally controlled by a complex consisting of TEA domain transcription factors (TEADs), forkhead box M1 (FoxM1), and yes-associated protein (YAP). Surprisingly, CEP55 did not significantly affect HCC cell proliferation but supported migration in conjunction with α‐catenin. Together, the enrichment of pro-migratory CEP55 in HCC cells is mediated by two mechanisms: transcriptional activation via the FoxM1/TEAD/YAP as well as the cytoplasmic stabilization through interaction with the AJ protein α‐catenin.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Thomas Ruppert

LAB HEAD: Thomas Ruppert

PROVIDER: PXD039222 | Pride | 2023-07-20

REPOSITORIES: Pride

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			Action	DRS
	20-175.pptx	Other
	OTEX_20201223_19-163_BH_04_20-175-1.raw	Raw
	OTEX_20201223_19-163_BH_06_20-175-2.raw	Raw
	OTEX_20201223_19-163_BH_08_20-175-3.raw	Raw
	OTEX_20201223_19-163_BH_10_20-175-4.raw	Raw

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α-catenin interaction with YAP/FoxM1/TEAD-induced CEP55 supports liver cancer cell migration.

Tang Yingyue Y Thiess Lena L Weiler Sofia M E SME Tóth Marcell M Rose Fabian F Merker Sabine S Ruppert Thomas T Schirmacher Peter P Breuhahn Kai K

Cell communication and signaling : CCS 20230628 1

<h4>Background</h4>Adherens junctions (AJs) facilitate cell-cell contact and contribute to cellular communication as well as signaling under physiological and pathological conditions. Aberrant expression of AJ proteins is frequently observed in human cancers; however, how these factors contribute to tumorigenesis is poorly understood. In addition, for some factors such as α-catenin contradicting data has been described. In this study we aim to decipher how the AJ constituent α-catenin contribute ...[more]

PMID: 37381005

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Project description:Background: Negative-pressure wound therapy has become widely available in modern chronic wound cares. Accelerated keratinocyte (HaCaT cell) movements and decreased E-cadherin expressions induced by the applied negative pressure gradient of 125 mmHg (NP) have been reported in previous studies. However, the molecular mechanism for E-cadherin regulations under NP remains unexplored. We highlighted the signal transduction involved in NP-induced E-cadherin regulation for keratinocytes in the study. Results: Microarray results showed that catenin 1 (CTNND1) gene, the gene encoding the p120-catenin (p120ctn) in cell-cell junctions, was significantly (p = 0.0005) upregulated in HaCaT cells under NP for 12 hours in comparison with those at ambient pressure (AP). Cell fractionations and immunoblotting data showed that NP increased p120ctn phosphorylation, and resulted in p120ctn translocation from the plasma membrane to the cytoplasm. Fluorescent stains suggested that NP diminished the co-localization of p120ctn and E-cadherin on the plasma membrane. Similar phenomenon was also observed in the cells with overexpressed p120ctn at NP. Interestingly, overexpression of dN- p120ctn, a deletion mutant of p120ctn without the N-terminal phosphorylation sites, restored the adherens junctions (AJ) at NP. Knockdown of p120ctn with lentiviral small hairpin RNA not only diminished E-cadherin expressions but also accelerated cell movement at AP. Conclusions: Phosphorylation of p120ctn is endowed to respond rapidly to NP and contributes to the AJ disassembly. This NP-induced E-cadherin downregulation can possibly accelerate wound-healing process. Conclusions: Phosphorylation of p120ctn is endowed to respond rapidly to NP and contributes to the AJ disassembly. This NP-induced E-cadherin downregulation can possibly accelerate wound-healing process. HaCaT cells under negative pressure (NP) gradient of 125 mmHg for 12 hours in comparison with those at ambient pressure (AP) were tested for RNA extraction and hybridization on Affymetrix microarrays. The experiments have been biological replicated three times. The differential expression gene between NP and AP were selected and validated with qPCR method.