Subtle Protective Roles of Clusterin in Gastric Metaplasia After Acute Oxyntic Atrophy

Vange, Pål; Bruland, Torunn; Munkvold, Bjørn; Røyset, Elin Synnøve; Gleave, Martin; Bakke, Ingrid

doi:10.1016/j.jcmgh.2018.09.013

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…The mutant corpus showed increased levels of multiple canonical SPEM transcripts Cftr, Pigr, Muc13, Dmbt1, Wfdc2, Gda, Clu, Plaur, Slc5a1, and Lgals4 ( Figure 11 , D ), as observed previously in multiple models of gastric cancer. 35 , 40 , 41 , 42 , 43 We confirmed upregulation of protein levels of VIL1, PIGR, and CD44 in our model. Gastric stem or progenitor cells have been proposed to be candidates for cancer stem cells, a possible source of cancer initiation.…”

Section: Resultssupporting

confidence: 81%

Elevated Protein Kinase A Activity in Stomach Mesenchyme Disrupts Mesenchymal-epithelial Crosstalk and Induces Preneoplasia

Puri

Grimmett

Faraj

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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Section: Resultssupporting

confidence: 81%

Elevated Protein Kinase A Activity in Stomach Mesenchyme Disrupts Mesenchymal-epithelial Crosstalk and Induces Preneoplasia

Puri

Grimmett

Faraj

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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“…Furthermore, ulcer-associated cell linage (UACL) has also been viewed as similar reparative linages and is observed in reparative processes along the gastrointestinal tract, including at the edges of gastric ulcers [56] and also in inflammatory bowel disease [57,58]. Also, one of the highly expressed markers of gastric SPEM, clusterin, seems to have subtle protective roles on oxyntic mucosa [59]. These observations combined suggest that SPEM should not be considered merely a preneoplastic lesion.…”

Section: Discussionmentioning

confidence: 99%

Gastric Corpus Mucosal Hyperplasia and Neuroendocrine Cell Hyperplasia, but not Spasmolytic Polypeptide-Expressing Metaplasia, Is Prevented by a Gastrin Receptor Antagonist in H+/K+ATPase Beta Subunit Knockout Mice

Aasarød

Stunes

Sandvik

et al. 2020

IJMS

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Proton pump inhibitor use is associated with an increased risk of gastric cancer, which may be mediated by hypergastrinemia. Spasmolytic polypeptide-expression metaplasia (SPEM) has been proposed as a precursor of gastric cancer. We have examined the effects of the gastrin receptor antagonist netazepide (NTZ) or vehicle on the gastric corpus mucosa of H+/K+ATPase beta subunit knockout (KO) and wild-type (WT) mice. The gastric corpus was evaluated by histopathology, immunohistochemistry (IHC), in situ hybridization (ISH) and whole-genome gene expression analysis, focusing on markers of SPEM and neuroendocrine (NE) cells. KO mice had pronounced hypertrophy, intra- and submucosal cysts and extensive expression of SPEM and NE cell markers in the gastric corpus, but not in the antrum. Numerous SPEM-related genes were upregulated in KO mice compared to WT mice. NTZ reduced hypertrophia, cysts, inflammation and NE hyperplasia. However, NTZ neither affected expression of SPEM markers nor of SPEM-related genes. In conclusion, NTZ prevented mucosal hypertrophy, cyst formation and NE cell hyperplasia but did not affect SPEM. The presence of SPEM seems unrelated to the changes caused by hypergastrinemia in this animal model.

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“…[ 5 ] Studies have implicated that CLU play important oncogenic roles in many cancers. [ 6,7 ] CLU is reported to be up‐regulated in breast cancers [ 6,8 ] and other cancers, including prostate, [ 9–12 ] gastric, [ 13,14 ] pancreatic, [ 15 ] colon, [ 16,17 ] and head and neck. [ 18 ] Previous studies have revealed many CLU's downstream targets in cancer, including those for inhibition of cell death pathways and modulation of pro‐survival signaling to promote cell growth.…”

Section: Introductionmentioning

confidence: 99%

Inhibition Lysosomal Degradation of Clusterin by Protein Kinase D3 Promotes Triple‐Negative Breast Cancer Tumor Growth

Liu

Zhou

et al. 2021

Advanced Science

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Triple negative breast cancer (TNBC), with its lack of targeted therapies, shows the worst mortality rate among all breast cancer subtypes. Clusterin (CLU) is implicated to play important oncogenic roles in cancer via promoting various downstream oncogenic pathways. Here, protein kinase D3 (PRKD3) is defined to be a key regulator of CLU in promoting TNBC tumor growth. Mechanically, PRKD3 with kinase activity binding to CLU is critical for CLU protein stability via inhibiting CLU's lysosomal distribution and degradation. CLU and PRKD3 protein level are significantly elevated and positively correlated in collected TNBC tumor samples. CLU silencer (OGX‐011) and PRKDs inhibitor (CRT0066101) can both result in impressive tumor growth suppression in vitro and in vivo, suggesting targeting CLU and its key regulator‐PRKD3 are promisingly efficient against TNBC. Finally, secreted CLU (sCLU) is found to be elevated in serums from TNBC patients and reduced in serum from TNBC murine models post OGX‐011 and/or CRT0066101 treatment, suggesting serum sCLU is a promising blood‐based biomarker for clinical management of TNBC. Taken together, this study provides a thorough molecular basis as well as preclinical evidences for targeting CLU pathway as a new promising strategy against TNBC via revealing PRKD3 as the key regulator of CLU in TNBC.

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Subtle Protective Roles of Clusterin in Gastric Metaplasia After Acute Oxyntic Atrophy

Cited by 4 publications

References 10 publications

Elevated Protein Kinase A Activity in Stomach Mesenchyme Disrupts Mesenchymal-epithelial Crosstalk and Induces Preneoplasia

Elevated Protein Kinase A Activity in Stomach Mesenchyme Disrupts Mesenchymal-epithelial Crosstalk and Induces Preneoplasia

Gastric Corpus Mucosal Hyperplasia and Neuroendocrine Cell Hyperplasia, but not Spasmolytic Polypeptide-Expressing Metaplasia, Is Prevented by a Gastrin Receptor Antagonist in H+/K+ATPase Beta Subunit Knockout Mice

Inhibition Lysosomal Degradation of Clusterin by Protein Kinase D3 Promotes Triple‐Negative Breast Cancer Tumor Growth

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