Elevated expression of GNAS promotes breast cancer cell proliferation and migration via the PI3K/AKT/Snail1/E-cadherin axis

Jin, Xiaoxiang; Zhu, Lihua; Cui, Zhuhong; Tang, Jing; Xie, Mingjun; Ren, Guosheng

doi:10.1007/s12094-019-02042-w

Cited by 47 publications

(42 citation statements)

References 31 publications

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“…There are 41 genes with the most hemimethylation in tumor DNA, see Table 9. Among these genes, TP73 [18][19][20], GNAS [21][22][23][24][25], and NOTCH1 [26,27] are notable ones with known relations to cancer. Table 9 shows that among these 41 genes, 1 is a tumor suppressor (WT1), 3 are oncogenes (GNAS, NOTCh1, and PRDM16), and of those 3, 2 are translocated cancer genes (NOTCH1 and PRDM16).…”

Section: Resultsmentioning

confidence: 99%

Statistical and Bioinformatic Analysis of Hemimethylation Patterns in Lung Cancer

Sun

Zane

Fulton

et al. 2020

Preprint

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Background: DNA methylation is an epigenetic event involving the addition of a methyl-group to a cytosine-guanine base pair (i.e., CpG site). It is associated with different cancers. Our research focuses on studying lung cancer hemimethylation, which refers to methylation occurring on only one of the two DNA strands. Many studies often assume that methylation occurs on both DNA strands at a CpG site. However, recent publications show the existence of hemimethylation and its impact. It is important to identify cancer hemimethylation patterns. Methods: In this paper, we use the Wilcoxon signed rank test to identify hemimethylated CpG sites based on publicly available lung cancer methylation sequencing data. We then identify two types of hemimethylated CpG clusters, regular and polarity clusters, and genes with large numbers of hemimethylated sites. Highly hemimethylated genes are then studied for their biological interactions using available bioinformatics tools. Results: In this paper, we have conducted the first-ever in-depth investigation of hemimethylation for lung cancer. Our results show that hemimethylation does exist in lung cells either as singletons or clusters. Most clusters contain only 2 or 3 CpG sites. Polarity clusters are much shorter than regular clusters and appear less frequently. The majority of clusters found in tumor samples have no overlap with clusters found in normal samples, and vice versa. Several genes that are known to be associated with cancer are hemimethylated differently between the cancerous and normal samples. Furthermore, highly hemimethylated genes exhibit many different interactions with other genes that may be associated with cancer. Hemimethylation has diverse patterns and frequencies that are comparable between normal and tumorous cells. Therefore, hemimethylation may be related to both normal and tumor cell development. Conclusions: Our research has identified CpG clusters and genes that are hemimethylated in normal and lung tumor samples. Due to the potential impact of hemimethylation on gene expression and cell function, these clusters and genes may be important to advance our understanding of the development and progression of lung cancer.

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Section: Resultsmentioning

confidence: 99%

Statistical and Bioinformatic Analysis of Hemimethylation Patterns in Lung Cancer

Sun

Zane

Fulton

et al. 2020

Preprint

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“…There are 41 genes with the most hemimethylation in tumor DNA, see Table 9. Among these genes, TP73 [15][16][17], GNAS [18][19][20][21][22], and NOTCH1 [23,24] are notable ones with known relations to cancer. Table 9 shows that among these 41 genes, one is a tumor suppressor (WT1), three are oncogenes (GNAS, NOTCH1, and PRDM16), and of those three, two are translocated cancer genes (NOTCH1 and PRDM16).…”

Section: Methodsmentioning

confidence: 99%

Statistical and Bioinformatic Analysis of Hemimethylation Patterns in Non-Small Cell Lung Cancer

Sun

Zane

Fulton

et al. 2020

Preprint

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Background: DNA methylation is an epigenetic event involving the addition of a methyl-group to a cytosine-guanine base pair (i.e., CpG site). It is associated with different cancers. Our research focuses on studying non-small cell lung cancer hemimethylation, which refers to methylation occurring on only one of the two DNA strands. Many studies often assume that methylation occurs on both DNA strands at a CpG site. However, recent publications show the existence of hemimethylation and its significant impact. Therefore, it is important to identify cancer hemimethylation patterns. Methods: In this paper, we use the Wilcoxon signed rank test to identify hemimethylated CpG sites based on publicly available non-small cell lung cancer methylation sequencing data. We then identify two types of hemimethylated CpG clusters, regular and polarity clusters, and genes with large numbers of hemimethylated sites. Highly hemimethylated genes are then studied for their biological interactions using available bioinformatics tools. Results: In this paper, we have conducted the first-ever investigation of hemimethylation in lung cancer. Our results show that hemimethylation does exist in lung cells either as singletons or clusters. Most clusters contain only two or three CpG sites. Polarity clusters are much shorter than regular clusters and appear less frequently. The majority of clusters found in tumor samples have no overlap with clusters found in normal samples, and vice versa. Several genes that are known to be associated with cancer are hemimethylated differently between the cancerous and normal samples. Furthermore, highly hemimethylated genes exhibit many different interactions with other genes that may be associated with cancer. Hemimethylation has diverse patterns and frequencies that are comparable between normal and tumorous cells. Therefore, hemimethylation may be related to both normal and tumor cell development. Conclusions: Our research has identified CpG clusters and genes that are hemimethylated in normal and lung tumor samples. Due to the potential impact of hemimethylation on gene expression and cell function, these clusters and genes may be important to advance our understanding of the development and progression of non-small cell lung cancer.

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“…The cAMP-PKA signaling has been associated to tumor-promoting effects in several cancer types via the activation of diverse downstream targets [72]. In particular, cAMP-PKA signaling has been shown to drive tumorigenesis and promote cell proliferation and migration in breast cancer through the activation of Src, PI3K/AKT, and GSK3/βcathenin pathways [73][74][75]. In pancreatic carcinogenesis, salt inducible kinases (SIK) were recently identified as critical tumor suppressors inhibited by GNAS signaling [76].…”

Section: Gnas and Krasmentioning

confidence: 99%

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights

Mas

Lupinacci

Cros

et al. 2021

IJMS

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Intraductal papillary mucinous neoplasms (IPMN) are common and one of the main precursor lesions of pancreatic ductal adenocarcinoma (PDAC). PDAC derived from an IPMN is called intraductal papillary mucinous carcinoma (IPMC) and defines a subgroup of patients with ill-defined specificities. As compared to conventional PDAC, IPMCs have been associated to clinical particularities and favorable pathological features, as well as debated outcomes. However, IPMNs and IPMCs include distinct subtypes of precursor (gastric, pancreato-biliary, intestinal) and invasive (tubular, colloid) lesions, also associated to specific characteristics. Notably, consistent data have shown intestinal IPMNs and associated colloid carcinomas, defining the “intestinal pathway”, to be associated with less aggressive features. Genomic specificities have also been uncovered, such as mutations of the GNAS gene, and recent data provide more insights into the mechanisms involved in IPMCs carcinogenesis. This review synthetizes available data on clinical-pathological features and outcomes associated with IPMCs and their subtypes. We also describe known genomic hallmarks of these lesions and summarize the latest data about molecular processes involved in IPMNs initiation and progression to IPMCs. Finally, potential implications for clinical practice and future research strategies are discussed.

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Elevated expression of GNAS promotes breast cancer cell proliferation and migration via the PI3K/AKT/Snail1/E-cadherin axis

Cited by 47 publications

References 31 publications

Statistical and Bioinformatic Analysis of Hemimethylation Patterns in Lung Cancer

Statistical and Bioinformatic Analysis of Hemimethylation Patterns in Lung Cancer

Statistical and Bioinformatic Analysis of Hemimethylation Patterns in Non-Small Cell Lung Cancer

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights

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