Increased Variance in Germline Allele-Specific Expression of APC Associates With Colorectal Cancer

Curia, Maria Cristina; Iure, Sabrina De; Lellis, Laura De; Veschi, Serena; Mammarella, Sandra; White, Marquitta J.; Bartlett, Jacquelaine; Iorio, Angelo Di; Amatetti, Cristina; Lombardo, Marco; Gregorio, Patrizia Di; Battista, Pasquale; Mariani–Costantini, Renato; Williams, Scott M.; Cama, Alessandro

doi:10.1053/j.gastro.2011.09.048

Cited by 18 publications

(22 citation statements)

References 32 publications

(73 reference statements)

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“…However, there are some differences between BCL7B and other tumor suppressors. For example, the Rb gene, which encodes the retinoblastoma (RB) protein, primarily functions to modulate the G 1 /S-phase cell cycle checkpoint [64] , [65] , [85] , whereas BCL7B knockdown increased the rate of G 1 arrest. This dissimilarity is further reflected by the finding that BCL7B knockdown does not induce hyperproliferation.…”

Section: Discussionmentioning

confidence: 99%

The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway

et al. 2015

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Human BCL7 gene family consists of BCL7A, BCL7B, and BCL7C. A number of clinical studies have reported that BCL7 family is involved in cancer incidence, progression, and development. Among them, BCL7B, located on chromosome 7q11.23, is one of the deleted genes in patients with Williams-Beuren syndrome. Although several studies have suggested that malignant diseases occurring in patients with Williams-Beuren syndrome are associated with aberrations in BCL7B, little is known regarding the function of this gene at the cellular level. In this study, we focused on bcl-7, which is the only homolog of BCL7 gene family in Caenorhabditis elegans, and analyzed bcl-7 deletion mutants. As a result, we found that bcl-7 is required for the asymmetric differentiation of epithelial seam cells, which have self-renewal properties as stem cells and divide asymmetrically through the WNT pathway. Distal tip cell development, which is regulated by the WNT pathway in Caenorhabditis elegans, was also affected in bcl-7-knockout mutants. Interestingly, bcl-7 mutants exhibited nuclear enlargement, reminiscent of the anaplastic features of malignant cells. Furthermore, in KATOIII human gastric cancer cells, BCL7B knockdown induced nuclear enlargement, promoted the multinuclei phenotype and suppressed cell death. In addition, this study showed that BCL7B negatively regulates the Wnt-signaling pathway and positively regulates the apoptotic pathway. Taken together, our data indicate that BCL7B/BCL-7 has some roles in maintaining the structure of nuclei and is involved in the modulation of multiple pathways, including Wnt and apoptosis. This study may implicate a risk of malignancies with BCL7B-deficiency, such as Williams-Beuren syndrome.

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Section: Discussionmentioning

confidence: 99%

The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway

et al. 2015

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“…Another mechanism of inactivation is a decrease in transcript expression, as previously described [185,186], in which APC showed a reduced germline expression regardless of the presence of the mutation.…”

Section: Major Colorectal Adenomatousmentioning

confidence: 83%

Molecular Aspects of Colorectal Adenomas: The Interplay among Microenvironment, Oxidative Stress, and Predisposition

Aceto

Catalano

Curia

2020

BioMed Research International

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The development of colorectal cancer (CRC) is a multistep process initiated by a benign polyp that has the potential to evolve into in situ carcinoma through the interactions between environmental and genetic factors. CRC incidence rates are constantly increased for young adult patients presenting an advanced tumor stage. The majority of CRCs arise from colonic adenomas originating from aberrant cell proliferation of colon epithelium. Endoscopic polypectomy represents a tool for early detection and removal of polyps, although the occurrence of cancers after negative colonoscopy shows a significant incidence. It has long been recognized that the aberrant regulation of Wingless/It (Wnt)/β-Catenin signaling in the pathogenesis of colorectal cancer is supported by its critical role in the differentiation of stem cells in intestinal crypts and in the maintenance of intestinal homeostasis. For this review, we will focus on the development of adenomatous polyps through the interplay between renewal signaling in the colon epithelium and reactive oxygen species (ROS) production. The current knowledge of molecular pathology allows us to deepen the relationships between oxidative stress and other risk factors as lifestyle, microbiota, and predisposition. We underline that the chronic inflammation and ROS production in the colon epithelium can impair the Wnt/β-catenin and/or base excision repair (BER) pathways and predispose to polyp development. In fact, the coexistence of oxidative DNA damage and errors in DNA polymerase can foster C>T transitions in various types of cancer and adenomas, leading to a hypermutated phenotype of tumor cells. Moreover, the function of Adenomatous Polyposis Coli (APC) protein in regulating DNA repair is very important as therapeutic implication making DNA damaging chemotherapeutic agents more effective in CRC cells that tend to accumulate mutations. Additional studies will determine whether approaches based on Wnt inhibition would provide long-term therapeutic value in CRC, but it is clear that APC disruption plays a central role in driving and maintaining tumorigenesis.

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“…In colorectal cancer, LOH preferentially affects the normal allele of the well-known tumor suppressor APC, and the risk allele linked to disease is usually retained [3] . Allele-specific expression analysis of APC has been proposed to be an important indicator of pathogenicity of familial adenomatous polyposis patients without APC mutations [11] . In addition to APC, allele-specific expression of TGFBR1 which results in reduced expression of the gene also confers an increased risk of colorectal cancer [12] .…”

Section: Research Highlightmentioning

confidence: 99%

Allele imbalance in the transcriptome of human hepatocellular carcinoma: stress-induced gene plays a role

Liu¹,

Guan

2014

Sci Proc

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The two alleles of a gene are usually expressed equally in a normal cell, however, high incidence of allele-specific imbalance is frequently observed in cancer cells. Chromosomal regions with recurrent allele-specific imbalance usually harbor risk alleles and critical genes associated with cancer susceptibility and progression. With the development of large scale transcriptome sequencing technology, systematic analysis of the allele imbalance in the cancer transcriptome could be achieved at the single nucleotide resolution. In the April 2014 issue of Gastroenterology, we reported that the allele-specific imbalance of Oxidative Stress Induced Growth Inhibitor 1 (OSGIN1) can significantly contribute to the progression of HCC. OSGIN1 is a stress-induced pro-apoptotic protein. By validating the sequencing results in a cohort of HCC patients, we found the variant 438H form of OSGIN1 was specifically overrepresented in the tumor tissues. Functional studies indicated that OSGIN1 has strong tumor suppressive function in HCC both in vitro and in vivo. The pro-apoptotic function of the variant form of OSGIN1 was found to be less potent than the wild-type form, and the functional defects might be due to its poor efficiency to localize to the mitochondria. Clinical pathological analysis further revealed that the expression and genotype of OSGIN1 are closely associated with the prognosis of HCC patients. Taken together, our study linked the stress-induced genes with allele imbalance in HCC transcriptome, and proposed OSGIN1 to be an important tumor suppressor gene in the progression of HCC. Further characterization of OSGIN1 might help predict the prognosis of HCC patients and their responses to chemotherapeutic drugs.To cite this article: Ming Liu, et al. Allele imbalance in the transcriptome of human hepatocellular carcinoma: stress-induced gene plays a role. Sci Proc 2014; 1: e382.

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Increased Variance in Germline Allele-Specific Expression of APC Associates With Colorectal Cancer

Cited by 18 publications

References 32 publications

The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway

The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway

Molecular Aspects of Colorectal Adenomas: The Interplay among Microenvironment, Oxidative Stress, and Predisposition

Allele imbalance in the transcriptome of human hepatocellular carcinoma: stress-induced gene plays a role

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