Pathophysiology of the Desmo-Adhesome

Celentano, Antonio; Mignogna, Michele Davide; McCullough, Michael; Cirillo, Nicola

doi:10.1002/jcp.25515

Cited by 11 publications

(4 citation statements)

References 165 publications

(180 reference statements)

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“…2c ). Moreover, according to previous reports, PKP3 is dysregulated in lung cancer [ 11 ]. Therefore, we analyzed the correlation between SOX30 and PKP3 and found that there is no correlation between the two (Additional file 4 : Figure S3a).…”

Section: Discussionmentioning

confidence: 76%

“…In the process of cancer development, cell junction molecules play a critical role in inhibiting tumor growth and metastasis [ 6 – 10 ]. Previous evidence revealed that desmosomal proteins, as a member of cell junction molecules, are deregulated in various cancers, including lung cancer [ 11 ]. In lung cancer, different members of desmosome genes have different roles in tumor progression.…”

Section: Introductionmentioning

confidence: 99%

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SOX30 is a key regulator of desmosomal gene suppressing tumor growth and metastasis in lung adenocarcinoma

Hao

Han

et al. 2018

J Exp Clin Cancer Res

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BackgroundThe expression of desmosomal genes in lung adenocarcinoma and lung squamous carcinoma is different. However, the regulatory mechanism of desmosomal gene expression in lung adenocarcinoma and lung squamous carcinoma remains unknown.MethodsThe correlation between expression of desmosomal gene expression and SOX30 expression were analyzed by bioinformatics. The expression of SOX30, DSP, JUP and DSC3 were detected in lung cancer cell lines, lung tissues of mice and patients’ tissues by qPCR, WB, Immunofluorescence and Immunohistochemistry. A chromatin Immunoprecipitation assay was used to investigate the mechanisms of the SOX30 regulation on desmosomal gene expression. In vitro proliferation, migration and invasion assays, and an in vivo nude mice model were utilized to assess the important role of desmosomal genes on SOX30-induced tumor suppression. A WB assay and TOP/FOP flash reporter assay was used to investigate the downstream pathway regulated by the SOX30-desmosomal gene axis. A chemical carcinogenic model of SOX30-knockout mice was generated to confirm the role of the SOX30-desmosomal gene axis in tumorigenesis.ResultsThe expression of desmosomal genes were upregulated by SOX30 in lung adenocarcinoma but not in lung squamous carcinoma. Further mechanism studies showed that SOX30 acts as a key transcriptional regulator of desmosomal genes by directly binding to the ACAAT motif of desmosomal genes promoter region and activating their transcription in lung adenocarcinoma. Knockdown of the expression of related desmosomal genes by miRNA significantly attenuated the inhibitory effect of SOX30 on cell proliferation, migration and invasion in vitro and on tumor growth and metastasis in vivo. In addition, knockout of SOX30 promotes lung tumor development and loss the inhibition of desmosomal genes on downstream Wnt and ERK signal in urethane-induced lung carcinogenesis in SOX30-knockout mice.ConclusionsOverall, these findings demonstrate for the first time that SOX30 acts as a master switch of desmosomal genes, inhibits lung adenocarcinoma cell proliferation, migration and invasion by activating the transcription of desmosomal genes. This study provides novel insights on the regulatory mechanism of desmosomal genes in lung adenocarcinoma.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0778-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

SOX30 is a key regulator of desmosomal gene suppressing tumor growth and metastasis in lung adenocarcinoma

Hao

Han

et al. 2018

J Exp Clin Cancer Res

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“…Ductal branching is established via NF-ĸB signaling, a downstream target of the ectodysplasin pathway ( 108 ). The increase in branching observed in mouse models of EDAR V370A ( 30 , 31 , 44 ) is likely the result of the EDA / EDAR /NF-ĸB pathway’s influence on the proteins that modulate the strength of the junctions that adhere the myoepithelial cells of the mammary ducts ( 109 – 111 ) ( Fig. 2 C – E ), facilitating or hindering branching during morphogenesis ( 112 ).…”

Section: Edar V370a ’S Influence On Ductal Branchingmentioning

confidence: 99%

Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk

Hlusko

Carlson

Chaplin

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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SignificanceThe frequency of the human-specific EDAR V370A isoform is highly elevated in North and East Asian populations. The gene is known to have several pleiotropic effects, among which are sweat gland density and ductal branching in the mammary gland. The former has led some geneticists to argue that the near-fixation of this allele was caused by selection for modulation of thermoregulatory sweating. We provide an alternative hypothesis, that selection instead acted on the allele’s effect of increasing ductal branching in the mammary gland, thereby amplifying the transfer of critical nutrients to infants via mother’s milk. This is likely to have occurred during the Last Glacial Maximum when a human population was genetically isolated in the high-latitude environment of the Beringia.

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“…Cell junction molecules such as desmosomes play a crucial role in inhibiting tumor growth and motility via metastasis processes [182][183][184]. Desmosomal proteins are shown to be deregulated in a variety of cancers, including lung cancer [185]. Moreover, they can serve as independent prognostic and diagnostic markers, such as is the case, for instance, with plakophilin 1 (PKP1) in LSCC [186,187], PKP3 and its tumor growth promotion in lung cancer [188], and the decreased levels of desmocolin 1 (DSC1) in NSCLC [189], which are shown to be associated with a poor prognosis.…”

Section: Sox30mentioning

confidence: 99%

Role of SOX Protein Groups F and H in Lung Cancer Progression

Olbromski¹,

Podhorska‐Okołów

Dzięgiel

2020

Cancers

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The SOX family proteins are proved to play a crucial role in the development of the lymphatic ducts and the cardiovascular system. Moreover, an increased expression level of the SOX18 protein has been found in many malignances, such as melanoma, stomach, pancreatic breast and lung cancers. Another SOX family protein, the SOX30 transcription factor, is responsible for the development of male germ cells. Additionally, recent studies have shown its proapoptotic character in non-small cell lung cancer cells. Our preliminary studies showed a disparity in the amount of mRNA of the SOX18 gene relative to the amount of protein. This is why our attention has been focused on microRNA (miRNA) molecules, which could regulate the SOX18 gene transcript level. Recent data point to the fact that, in practically all types of cancer, hundreds of genes exhibit an abnormal methylation, covering around 5–10% of the thousands of CpG islands present in the promoter sequences, which in normal cells should not be methylated from the moment the embryo finishes its development. It has been demonstrated that in non-small-cell lung cancer (NSCLC) cases there is a large heterogeneity of the methylation process. The role of the SOX18 and SOX30 expression in non-small-cell lung cancers (NSCLCs) is not yet fully understood. However, if we take into account previous reports, these proteins may be important factors in the development and progression of these malignancies.

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Pathophysiology of the Desmo-Adhesome

Cited by 11 publications

References 165 publications

SOX30 is a key regulator of desmosomal gene suppressing tumor growth and metastasis in lung adenocarcinoma

SOX30 is a key regulator of desmosomal gene suppressing tumor growth and metastasis in lung adenocarcinoma

Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk

Role of SOX Protein Groups F and H in Lung Cancer Progression

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