Human stomach-specific gene, CA11, is down-regulated in gastric cancer

Shiozaki, Ken; Nakamori, Shoji; Tsujie, Masanori; Okami, Jiro; Yamamoto, Hirofumi; Nagano, Hiroaki; Dono, Keizo; Umeshita, Koji; Sakon, Masato; Furukawa, Hiroshi; Hiratsuka, Masahiro; Kasugai, Tsutomu; Ishiguro, Shingo; Monden, Morito

doi:10.3892/ijo.19.4.701

Cited by 37 publications

(68 citation statements)

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“…Toback and colleagues reported that GKN1 protects the antral mucosa and promotes healing by facilitating restitution and proliferation after injury (3). Interestingly, GKN1 is downregulated in Helicobacter pylori-infected gastric epithelial cells, and the loss of GKN1 expression is detected in gastric cancer tissues and precancerous lesions such as intestinal metaplasia (4,5). We also witnessed frequent loss of GKN1 expression in gastric cancers and confirmed tumor suppressor activity of GKN1 through a functional analysis (6).…”

Section: Introductionmentioning

confidence: 58%

GKN1–miR-185–DNMT1 Axis Suppresses Gastric Carcinogenesis through Regulation of Epigenetic Alteration and Cell Cycle

Yoon

Choi

et al. 2013

Clinical Cancer Research

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Purpose: Gastrokine 1 (GKN1) functions to protect the gastric antral mucosa and promotes healing by facilitating restoration and proliferation after injury. GKN1 is downregulated in Helicobacter pylori-infected gastric epithelial cells and loss of GKN1 expression is closely associated with gastric carcinogenesis, but underlying mechanisms of the tumor-suppressing effects of GKN1 remain largely unknown.Experimental Design: AGS, MKN1, MKN28 gastric cancer cells and HFE-145 immortalized nonneoplastic gastric mucosal cells were transfected with GKN1 or shGKN1. We conducted molecular and functional studies of GKN1 and miR-185 and investigated the mechanisms of alteration. We also analyzed epigenetic alterations in 80 gastric cancer tissues.Results: Restoration of GKN1 protein suppressed gastric cancer cell growth by inducing endogenous miR-185 that directly targets epigenetic effectors DNMT1 and EZH2 in gastric cancer cells. In addition, ectopic expression of GKN1 upregulated Tip60 and downregulated HDAC1 in an miR-185-independent manner, thereby inducing cell-cycle arrest by regulating cell-cycle proteins in gastric cancer cells. Notably, GKN1 expression was inversely correlated with DNMT1 and EZH2 expression in a subset of 80 gastric cancer tissues and various gastric cancer cell lines. Interestingly, it was found that GKN1 exerted a synergistic anticancerous effect with 5-fluorouracil on tumor cell growth, which suggests a possible therapeutic intervention method for gastric cancer.Conclusion: Our results show that GKN1 has an miR-185-dependent and -independent mechanism for chromatic and DNA epigenetic modification, thereby regulating the cell cycle. Thus, the loss of GKN1 function contributes to malignant transformation and proliferation of gastric epithelial cells in gastric carcinogenesis.

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Section: Introductionmentioning

confidence: 58%

GKN1–miR-185–DNMT1 Axis Suppresses Gastric Carcinogenesis through Regulation of Epigenetic Alteration and Cell Cycle

Yoon

Choi

et al. 2013

Clinical Cancer Research

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“…Expression of BRI 2 (a mutant from BRI gene family) is associated with a central nervous system syndrome whose pathologic, morphologic, and histologic features resemble that of Alzheimer's disease (5,6). Deficiency of CA11, which is specifically expressed in the stomach, is linked to gastric cancer (7). Mutation in the gene encoding ChM-I is related to chondrosarcoma, a malignant neoplasm of cartilage and bone (8).…”

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confidence: 99%

A Surfactant Protein C Precursor Protein BRICHOS Domain Mutation Causes Endoplasmic Reticulum Stress, Proteasome Dysfunction, and Caspase 3 Activation

Mulugeta

Nguyen

Russo

et al. 2005

Am J Respir Cell Mol Biol

238

224

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BRICHOS is a domain found in several proteins consisting of ‫ف‬ 100 amino acids with sequence and structural similarities. Mutations in BRICHOS domain have been associated with both degenerative and proliferative diseases in several nonpulmonary organs, although the pathogenic mechanisms are largely undefined. Recently, several mutations in surfactant protein C (SP-C) mapping to the BRICHOS domain located within the proprotein (proSP-C) have been linked to interstitial lung diseases. In vitro expression of one of these BRICHOS mutants, the exon 4 deletion (hSP-C Surfactant protein C (SP-C) is a small hydrophobic protein, found in pulmonary surfactant, initially identified upon isolation from bronchoalveolar lavage of a variety of mammalian species. SP-C is synthesized in alveolar type II cells as a 21-kD integral membrane precursor (proSP-C), which undergoes proteolytic C-and N-terminal cleavages as it is trafficked through the biosynthetic pathway from the Golgi complex, by way of small vesicles and multivesicular bodies, to the lumen of lamellar bodies, yielding a 3.7-kD mature peptide (1, 2). Together with other surfactant proteins and phospholipids contained in the lamellar body, SP-C is released into the alveolar space, via regulated secretion (1, 3), where it functions to modulate lung surface tension during the respiratory cycle.(Received in original form January 6, 2005 and in final form February 22, 2005) Correspondence and requests for reprints should be addressed to Surafel Mulugeta, Ph.D

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“…The nucleotide sequence of GKN1 shows the presence of two translation starting sites (ATG) however, only from the second ATG the gene would encode for a protein of 185 amino acids. Edman's degradation performed on native human GKN1 confirmed the assumption and showed that the protein contains in its N-terminal region a 20 amino acids extracellular signal peptide 3 ( Figure 1). …”

Section: Introductionmentioning

confidence: 62%

Human Gastrokine 1 and its anti-amyloidogenic properties

Stadio¹,

Altieri²,

Minopoli³

et al. 2017

J Neurol Neuromedicine

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Gastrokine 1 (GKN1) is a 18 kDa stomach protein highly expressed in normal gastric tissue but absent in gastric cancer. GKN1 plays its major role in maintaining gastric mucosal integrity. Because of the presence in its central region of a BRICHOS domain, GKN1 is characterized by multifunctional properties since it interacts and regulates the activity of several proteins. The BRICHOS domain consists of about 100 amino acids and has been found in protein families often associated with major human diseases like familial British and Danish dementia (BRI2) or respiratory distress syndrome (surfactant protein C) (SP-C), both associated with amyloid formation. It has been shown that BRICHOS is a chaperon domain that has the property of binding precursor protein regions with high β-sheet tendencies, thereby preventing them from amyloid formation. Like the BRICHOS domains from BRI2 and SP-C precursor (proSP-C), also GKN1 is able to prevent fibrils formation of amyloidbeta peptide (Aβ) and to interact with the C-terminal region of APP thus hindering the γ-secretase proteolytic sites. Indeed, amyloid is of great medical importance since it originates in several major fatal diseases such as Alzheimer, Parkinson and diabetes mellitus. The results collected until now on the BRICHOS properties of GKN1 and those from other BRICHOS suggest that the different amyloids recognized by BRICHOS should contain similar structural elements therefore, the BRICHOS domain represents a potential powerfull tool for therapeutic approaches against amyloid associated diseases.

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Human stomach-specific gene, CA11, is down-regulated in gastric cancer

Cited by 37 publications

References 0 publications

GKN1–miR-185–DNMT1 Axis Suppresses Gastric Carcinogenesis through Regulation of Epigenetic Alteration and Cell Cycle

GKN1–miR-185–DNMT1 Axis Suppresses Gastric Carcinogenesis through Regulation of Epigenetic Alteration and Cell Cycle

A Surfactant Protein C Precursor Protein BRICHOS Domain Mutation Causes Endoplasmic Reticulum Stress, Proteasome Dysfunction, and Caspase 3 Activation

Human Gastrokine 1 and its anti-amyloidogenic properties

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