Plakophilin-2 accelerates cell proliferation and migration through activating EGFR signaling in lung adenocarcinoma

Hao, Xianglin; Tian, Zhen; Han, Fangfang; Chen, Jianping; Gao, Liyun; Liu, Jinyi

doi:10.1016/j.prp.2019.152438

Cited by 23 publications

(23 citation statements)

References 16 publications

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“…Intriguingly, in PKP2-deficient myocytes a large number of transcripts associated with inflammatory responses were upregulated ( Perez-Hernandez et al, 2020 ). Consistently, PKP2 has been shown to regulate EGFR/p38MAPK and PKCα signaling pathways ( Bass-Zubek et al, 2008 ; Arimoto et al, 2014 ; Dubash et al, 2016 ; Hao et al, 2019 ), which can affect the transcription of genes that are altered in PKP2 knockout cardiomyocytes.…”

Section: Desmosomal Proteins As Effectors: Regulation Of Inflammationmentioning

confidence: 82%

“…In support, PKP2 knockdown reduced EGFR phosphorylation and attenuated EGFR-mediated signal activation, resulting in a significant decrease in proliferation and migration of breast cancer cells ( Arimoto et al, 2014 ). In lung adenocarcinoma, PKP2 knockdown suppressed proliferation as indicated by reduced numbers of cells in S phase ( Wu et al, 2021 ) whereas PKP2 overexpression led to enhanced proliferation and colony formation ( Hao et al, 2019 ). PKP2 is mainly expressed in cardiomyocytes and heterozygous mutations in the PKP2 gene are a common cause of ACM ( Gerull et al, 2004 ).…”

Section: Desmosomal Proteins As Effectors: Control Of Proliferationmentioning

confidence: 99%

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Desmosomes as Signaling Hubs in the Regulation of Cell Behavior

Müller

Hatzfeld

Keil

2021

Front. Cell Dev. Biol.

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Desmosomes are intercellular junctions, which preserve tissue integrity during homeostatic and stress conditions. These functions rely on their unique structural properties, which enable them to respond to context-dependent signals and transmit them to change cell behavior. Desmosome composition and size vary depending on tissue specific expression and differentiation state. Their constituent proteins are highly regulated by posttranslational modifications that control their function in the desmosome itself and in addition regulate a multitude of desmosome-independent functions. This review will summarize our current knowledge how signaling pathways that control epithelial shape, polarity and function regulate desmosomes and how desmosomal proteins transduce these signals to modulate cell behavior.

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Section: Desmosomal Proteins As Effectors: Regulation Of Inflammationmentioning

confidence: 82%

Section: Desmosomal Proteins As Effectors: Control Of Proliferationmentioning

confidence: 99%

Desmosomes as Signaling Hubs in the Regulation of Cell Behavior

Müller

Hatzfeld

Keil

2021

Front. Cell Dev. Biol.

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“…As early as the discovery of PKP2, researchers found that the expression level of PKP2 was significant different in tumors with varying degrees of differentiation [ 36 ]. High expression of PKP2 was also associated with the prognosis and promoted proliferation and invasion in gliomas and lung adenocarcinomas [ 37 , 38 ], suggesting that PKP2 could promote tumor progression. However, many studies have showed that PKP2 was decreased in some malignant tumors, such as gastric cancer and bladder cancer [ 39 , 40 ], and negatively correlated with the prognosis, proliferation and invasion of these tumors, indicating that PKP2 can also act as a tumor suppressor gene in malignant tumors.…”

Section: Discussionmentioning

confidence: 99%

“…We only explored the regulatory network, functional mechanism and immune infiltration of PKP2/3 in OC subsequently. In terms of potential mechanism, PKP2 could regulate the activity of Wnt/β-catenin in colon cancer-associated fibroblasts [54], and PKP2 promoted the proliferation and migration of lung cancer by activating EGFR signaling pathway [38]. In addition, PKP3 regulated autophagy and invasion of ovarian cancer through MAPK/JNK/ERK1/2/mTOR signaling pathway [13,14].…”

Section: Casesmentioning

confidence: 99%

Identification of PKP 2/3 as potential biomarkers of ovarian cancer based on bioinformatics and experiments

Gao

Guo

et al. 2020

Cancer Cell Int

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Background Plakophilins (PKPs) are widely involved in gene transcription, translation, and signal transduction, playing a crucial role in tumorigenesis and progression. However, the function and potential mechanism of PKP1/2/3 in ovarian cancer (OC) remains unclear. It’s of great value to explore the expression and prognostic values of PKP1/2/3 and their potential mechanisms, immune infiltration in OC. Methods The expression levels, prognostic values and genetic variations of PKP1/2/3 in OC were explored by various bioinformatics tools and databases, and PKP2/3 were selected for further analyzing their regulation network and immune infiltration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) enrichment were also conducted. Finally, the expression and prognosis of PKP2 were validated by immunohistochemistry. Results The expression level and prognosis of PKP1 showed little significance in ovarian cancer, and the expression of PKP2/3 mRNA and protein were upregulated in OC, showing significant correlations with poor prognosis of OC. Functional enrichment analysis showed that PKP2/3 and their correlated genes were significantly enriched in adaptive immune response, cytokine receptor activity, organization of cell–cell junction and extracellular matrix; KEGG analysis showed that PKP2/3 and their significantly correlated genes were involved in signaling pathways including cytokine-mediated signaling pathway, receptor signaling pathway and pathways in cancer. Moreover, PKP2/3 were correlated with lymphocytes and immunomodulators. We confirmed that high expression of PKP2 was significantly associated with advanced stage, poor differentiation and poor prognosis of OC patients. Conclusion Members of plakophilins family showed various degrees of abnormal expressions and prognostic values in ovarian cancer. PKP2/3 played crucial roles in tumorigenesis, aggressiveness, malignant biological behavior and immune infiltration of OC, and can be regarded as potential biomarker for early diagnosis and prognosis evaluation in OC.

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“…Plakophilin 2 participates in linking cadherins to intermediate filaments in the cytoskeleton and cardiac muscles. It has been shown to be associated with several types of cancers in humans (48). PKP2 regulates calcium signaling in cardiac muscles (49).…”

Section: Regulation Of Actin Cytoskeletonmentioning

confidence: 99%