Porcupine expression is associated with the expression of S100P and other cancer-related molecules in non-small cell lung carcinoma

Bartling, Babett; Rehbein, Grit; Simm, Andreas; Silber, Rolf-Edgar; Hofmann, Hans‐Stefan

doi:10.3892/ijo_00000582

Cited by 13 publications

(9 citation statements)

References 40 publications

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“…A recent paper investigating PORCN in Non Small Cell Lung Carcinoma illustrated that loss of PORCN downregulates S100P at the mRNA and protein levels in a β-catenin independent manner [28], similar to what we have shown for APEH. As PORCN is an integral ER membrane protein, it seems most likely that its loss disrupts an ER process.…”

Section: Discussionsupporting

confidence: 85%

“…These findings were extended in five additional breast cancer cell lines; RNAi-mediated knockdown of PORCN caused a statistically significant decrease in proliferation (Figure 1E) in each cell line tested. RNAi-mediated knockdown of PORCN has been reported to cause apoptosis in human lung cancer cells [27], although this finding could not be independently reproduced [28]. While we found a decrease in growth in a number of breast cancer cell lines, PORCN knockdown did not result in apoptosis or a shift in cell cycle distribution in any of the cancer lines tested (Figure S1B, and data not shown).…”

Section: Resultsmentioning

confidence: 58%

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PORCN Moonlights in a Wnt-Independent Pathway That Regulates Cancer Cell Proliferation

et al. 2012

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Porcupine (PORCN) is a membrane-bound O-acyl transferase that is required for the palmitoylation of Wnt proteins, and that is essential in diverse Wnt pathways for Wnt-Wntless (WLS) binding, Wnt secretion, and Wnt signaling activity. We tested if PORCN was required for the proliferation of transformed cells. Knockdown of PORCN by multiple independent siRNAs results in a cell growth defect in a subset of epithelial cancer cell lines. The growth defect is transformation-dependent in human mammary epithelial (HMEC) cells. Additionally, inducible PORCN knockdown by two independent shRNAs markedly reduces the growth of established MDA-MB-231 cancers in orthotopic xenografts in immunodeficient mice. Unexpectedly, the proliferation defect resulting from loss of PORCN occurs in a Wnt-independent manner, as it is rescued by re-expression of catalytically inactive PORCN, and is not seen after RNAi-mediated knockdown of the Wnt carrier protein WLS, nor after treatment with the PORCN inhibitor IWP. Consistent with a role in a Wnt-independent pathway, knockdown of PORCN regulates a distinct set of genes that are not altered by other inhibitors of Wnt signaling. PORCN protein thus appears to moonlight in a novel signaling pathway that is rate-limiting for cancer cell growth and tumorigenesis independent of its enzymatic function in Wnt biosynthesis and secretion.

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Section: Discussionsupporting

confidence: 85%

Section: Resultsmentioning

confidence: 58%

PORCN Moonlights in a Wnt-Independent Pathway That Regulates Cancer Cell Proliferation

et al. 2012

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“…These genes were involved in the regulation of cell growth, cell cycle, differentiation, apoptosis, adhesion, migration and tumor microenvironment. [23][24][25][26][27][28][29][30][31][32][33][34][35][36] Except GDA37 and CLMP, 38 the other genes have been proven to have important significance in tumor development, and many have critical roles in drug resistance. [39][40][41][42] For example, S100P, a 95 amino acid protein, acts as an autocrine growth and survival factor.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of DNA methylation and mRNA expression profiling reveals candidate genes associated with cisplatin resistance in non-small cell lung cancer

et al. 2014

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DNA methylation plays a critical role during the development of acquired chemoresistance. The aim of this study was to identify candidate DNA methylation drivers of cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC). The A549/DDP cell line was established by continuous exposure of A549 cells to increasing concentrations of DDP. Gene expression and methylation profiling were determined by high-throughput microarrays. Relationship of methylation status and DDP response was validated in primary tumor cell culture and the Cancer Genome Atlas (TCGA) samples. Cell proliferation, apoptosis, cell cycle, and response to DDP were determined in vitro and in vivo. A total of 372 genes showed hypermethylation and downregulation in A549/DDP cells, and these genes were involved in most fundamental biological processes. Ten candidate genes (S100P, GDA, WISP2, LOXL1, TIMP4, ICAM1, CLMP, HSP8, GAS1, BMP2) were selected, and exhibited varying degrees of association with DDP resistance. Low dose combination of 5-aza-2'-deoxycytidine (5-Aza-dC) and trichostatin A (TSA) reversed drug resistance of A549/DDP cells in vitro and in vivo, along with demethylation and restoration of expression of candidate genes (GAS1, TIMP4, ICAM1 and WISP2). Forced expression of GAS1 in A549/DDP cells by gene transfection contributed to increased sensitivity to DDP, proliferation inhibition, cell cycle arrest, apoptosis enhancement, and in vivo growth retardation. Together, our study demonstrated that a panel of candidate genes downregulated by DNA methylation induced DDP resistance in NSCLC, and showed that epigenetic therapy resensitized cells to DDP.

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“…It contains 2 EF-hand calcium-binding motifs (17) and involves in a series of cellular regulation processes, such as cell cycle progressions and differentiation (18). S100P was found to be one of the target genes studied in many cancers including NSCLC (19). The expression of S100P was associated with drug resistance, metastasis, and poor clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

Identification of miRNAs and differentially expressed genes in early phase non-small cell lung cancer

Tian

Liu²,

Pei

et al. 2016

Oncology Reports

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Abstract.To explore the potential therapeutic targets of early-stage non-small cell lung cancer (NSCLC), gene microarray analysis was conducted. The microarray data of NSCLC in stage IA, IB, IIA, and IIB (GSE50081), were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in IB vs. IA, IIA vs. IB, IIB vs. IIA were screened out via R. ToppGene Suite was used to get the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the DEGs. The GeneCoDis3 database and Cytoscape software were used to construct the transcriptional regulatory network. In total, 25, 17 and 14 DEGs were identified in IB vs. IA, IIA vs. IB, IIB vs. IIA of NSCLC, respectively. Some GO terms and pathways (e.g., extracellular space, alveolar lamellar body, bioactivation via cytochrome P450 pathway) were found significantly enriched in DEGs. Genes S100P, ALOX15B, CCL11, NLRP2, SERPINA3, FoxO4 and hsa-miR-491 may play important roles in the development of early-stage NSCLC. Thus, by bioinformatics analysis the key genes and biological processes involving in the development of early-stage NSCLC could be established, providing more potential references for the therapeutic targets.

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Porcupine expression is associated with the expression of S100P and other cancer-related molecules in non-small cell lung carcinoma

Cited by 13 publications

References 40 publications

PORCN Moonlights in a Wnt-Independent Pathway That Regulates Cancer Cell Proliferation

PORCN Moonlights in a Wnt-Independent Pathway That Regulates Cancer Cell Proliferation

Integrated analysis of DNA methylation and mRNA expression profiling reveals candidate genes associated with cisplatin resistance in non-small cell lung cancer

Identification of miRNAs and differentially expressed genes in early phase non-small cell lung cancer

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