Apoptosis Factor EI24/PIG8 Is a Novel Endoplasmic Reticulum–Localized Bcl-2–Binding Protein which Is Associated with Suppression of Breast Cancer Invasiveness

Zhao, Xinzhen; Ayer, Robert; Davis, Shannon L.; Ames, Sarah J.; Florence, Brian; Torchinsky, Cyrus; Liou, James S.; Shen, Lei; Spanjaard, Remco A.

doi:10.1158/0008-5472.can-04-3377

Cited by 58 publications

(74 citation statements)

References 27 publications

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“…It seems that nuclear sequestration might lead to growth advantage of the tumor. Loss of Ei24 expression as reported by Zhao et al 24 is associated with tumor invasiveness but not with the development of primary breast tumor. It was evident from Table 1 that some samples showed low Ei24 expression without any alterations of this gene.…”

Section: Cancer Geneticsmentioning

confidence: 55%

“…Investigations report localization of Ei24 in endoplasmic reticulum, mitochondrial and nuclear membranes. 24 Ei24 interacts with Bcl-2 in the cytoplasm to inhibit its antiapoptotic function. 24 The importance of nuclear localization of Ei24 is not clear.…”

Section: Cancer Geneticsmentioning

confidence: 99%

“…24 Ei24 interacts with Bcl-2 in the cytoplasm to inhibit its antiapoptotic function. 24 The importance of nuclear localization of Ei24 is not clear. It seems that nuclear sequestration might lead to growth advantage of the tumor.…”

Section: Cancer Geneticsmentioning

confidence: 99%

“…EI24, a p53-and etoposideinducible gene, interacts with Bcl-2 and regulates apoptosis. 23,24 The Bcl-2-binding domain of EI24 is encoded by the exons 3, 4 and 5. Frequent mutation (17%) of EI24 is reported in breast cancer 19 and is suggested to be associated with tumor invasiveness.…”

mentioning

confidence: 99%

“…Frequent mutation (17%) of EI24 is reported in breast cancer 19 and is suggested to be associated with tumor invasiveness. 24 However, involvement of EI24 in CACX is not yet studied. CHEK1 plays a significant role in DNA damage repair mechanism, by arresting damaged cells at the cell cycle checkpoints, and also inhibits the firing of replication origin during stalled replication.…”

mentioning

confidence: 99%

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Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: Clinical and prognostic implications

Mazumder

Mitra

Singh

et al. 2011

Intl Journal of Cancer

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To understand the importance of frequent deletion of chromosomal 11q23.3-24.3 region in cervical carcinogenesis, alterations (deletion/methylation/mutation/expression) of the candidate genes LOH11CR2A, EI24 and CHEK1 located in the region were analyzed in 29 cervical intraepithelial neoplasia (CIN), 112 cervical carcinoma (CACX) samples and two CACX cell lines. The deletion frequency of these genes was low in CIN than in CACX [CIN: CHEK1: 28%, EI24: 21%, LOH11CR2A: 15% and CACX: CHEK1: 51%, EI24: 41%, LOH11CR2A: 36%]. Similar trend was seen in promoter methylation of these genes [CIN: CHEK1: 10%, EI24: 3%, LOH11CR2A: 3% and CACX: CHEK1: 55%, EI24: 31%, LOH11CR2A: 14%]. Mutations of the genes are a rare event. Overall alterations (deletion and methylation) of CHEK1 and EI24 were associated with progression of CACX. Quantitative mRNA expression analysis showed reduced expression of the three genes in concordance to their molecular alterations. A shorter isoform of CHEK1 lacking exon 8, hence impaired in substrate binding capacity, was found in two samples. Immunohistochemical analysis showed nuclear expression of Chek1, p-Chek1 and Ei24 in tumor tissues, whereas the cell lines exhibited both nuclear and cytoplasmic expression of Chek1 and Ei24, as is also evident from Western blot analysis suggesting differential localization of the proteins. Alterations of CHEK1 and EI24 coupled with tumor stage and early sexual debut ( 19 years) predicted worst prognosis. Thus, our data suggest that inactivation of EI24 and CHEK1 through two independent mechanisms contributes to the development of CACX.Worldwide, cervical cancer (CACX) is one of the most deadly cancers among women and occupies second position among females in eastern India (Kolkata). 1 Infection by highrisk human papillomavirus (HPV) is a major cause of CACX 2 along with other etiological factors, such as use of oral contraceptives, precocious marriage, multiparity and smoking. 1,3 As HPV infections in most cases do not lead to cancer, and even a long latency period for the cancerous outcome in infected women suggests involvement of additional genetic alterations like functional inactivation of tumor suppressor genes (TSGs) or activation of oncogenes. 4 Investigations showing frequent chromosomal deletion in 11q23-q24 (20.4 Mb) in cervix, 5-7 breast, 8,9 lung, 10 colon 11 and ovarian 12 cancer and functional chromosome-transfer

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Section: Cancer Geneticsmentioning

confidence: 55%

Section: Cancer Geneticsmentioning

confidence: 99%

Section: Cancer Geneticsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: Clinical and prognostic implications

Mazumder

Mitra

Singh

et al. 2011

Intl Journal of Cancer

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Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: Its correlation with smoking history and chronic obstructive pulmonary disease

Sato

Arai²,

Kohno

et al. 2014

Int. J. Cancer

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The aim of this study was to clarify the significance of DNA methylation alterations during lung carcinogenesis. Infinium assay was performed using 139 paired samples of non-cancerous lung tissue (N) and tumorous tissue (T) from a learning cohort of patients with lung adenocarcinomas (LADCs). Fifty paired N and T samples from a validation cohort were also analyzed. DNA methylation alterations on 1,928 probes occurred in N samples relative to normal lung tissue from patients without primary lung tumors, and were inherited by, or strengthened in, T samples. Unsupervised hierarchical clustering using DNA methylation levels in N samples on all 26,447 probes subclustered patients into Cluster I (n = 32), Cluster II (n = 35) and Cluster III (n = 72). LADCs in Cluster I developed from the inflammatory background in chronic obstructive pulmonary disease (COPD) in heavy smokers and were locally invasive. Most patients in Cluster II were non-smokers and had a favorable outcome. LADCs in Cluster III developed in light smokers were most aggressive (frequently showing lymphatic and blood vessel invasion, lymph node metastasis and an advanced pathological stage), and had a poor outcome. DNA methylation levels of hallmark genes for each cluster, such as IRX2, HOXD8, SPARCL1, RGS5 and EI24, were again correlated with clinicopathological characteristics in the validation cohort. DNA methylation profiles reflecting carcinogenetic factors such as smoking and COPD appear to be established in non-cancerous lung tissue from patients with LADCs and may determine the aggressiveness of tumors developing in individual patients, and thus patient outcome.

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Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis

Uddin

Mamun

Labu

et al. 2018

Journal Cellular Physiology

119

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Autophagy is a preserved cytoplasmic self‐degradation process and endorses recycling of intracellular constituents into bioenergetics for the controlling of cellular homeostasis. Functional autophagy process is essential in eliminating cytoplasmic waste components and helps in the recycling of some of its constituents. Studies have revealed that neurodegenerative disorders may be caused by mutations in autophagy‐related genes and alterations of autophagic flux. Alzheimer’s disease (AD) is an irrevocable deleterious neurodegenerative disorder characterized by the formation of senile plaques and neurofibrillary tangles (NFTs) in the hippocampus and cortex. In the central nervous system of healthy people, there is no accretion of amyloid β (Aβ) peptides due to the balance between generation and degradation of Aβ. However, for AD patients, the generation of Aβ peptides is higher than lysis that causes accretion of Aβ. Likewise, the maturation of autophagolysosomes and inhibition of their retrograde transport creates favorable conditions for Aβ accumulation. Furthermore, increasing mammalian target of rapamycin (mTOR) signaling raises tau levels as well as phosphorylation. Alteration of mTOR activity occurs in the early stage of AD. In addition, copious evidence links autophagic/lysosomal dysfunction in AD. Compromised mitophagy is also accountable for dysfunctional mitochondria that raises Alzheimer’s pathology. Therefore, autophagic dysfunction might lead to the deposit of atypical proteins in the AD brain and manipulation of autophagy could be considered as an emerging therapeutic target. This review highlights the critical linkage of autophagy in the pathogenesis of AD, and avows a new insight to search for therapeutic target for blocking Alzheimer’s pathogenesis.

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Apoptosis Factor EI24/PIG8 Is a Novel Endoplasmic Reticulum–Localized Bcl-2–Binding Protein which Is Associated with Suppression of Breast Cancer Invasiveness

Abstract: Abstractp53 is a critical tumor suppressor which removes cells with DNA damage by regulating expression and activity of a select group of p53-induced genes

Cited by 58 publications

References 27 publications

Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: Clinical and prognostic implications

Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: Clinical and prognostic implications

Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: Its correlation with smoking history and chronic obstructive pulmonary disease

Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis

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