A Summary of the 2016 James W. Freston Conference of the American Gastroenterological Association: Intestinal Metaplasia in the Esophagus and Stomach: Origins, Differences, Similarities and Significance

Spechler, Stuart J.; Merchant, Juanita L.; Wang, Yichen; Chandrasoma, Parakrama; Fox, James G.; Genta, Robert M.; Goldenring, James R.; Hayakawa, Yoku; Kuipers, Ernst J.; Lund, P. Kay; McKeon, Frank; Mills, Jason C.; Odze, Robert D.; Peek, Richard M.; Pham, Thai H.; Que, Jianwen; Rustgi, Anil K.; Shaheen, Nicholas J.; Shivdasani, Ramesh A.; Souza, Rhonda F.; Störz, Peter; Todisco, Andrea; Wang, David H.; Wright, Nicholas A.

doi:10.1053/j.gastro.2017.05.050

Cited by 19 publications

(14 citation statements)

References 87 publications

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“…In regions where basal cells showed more uniform metaplasia ("established SPEM"), pS6 levels were lower. In addition, SPEM is thought to progress to (or predate) another, proliferative, pre-cancerous lesion, intestinal metaplasia (Yoshizawa et al, 2007;Correa & Piazuelo, 2012;Spechler et al, 2017) and to increase risk for progression to a cytologically atypical lesion, dysplasia, as well as to cancer itself. In the chronic case, SPEM is equivalent to the lesion pathologists call chronic atrophic gastritis (Rugge et al, 2008).…”

Section: Changes In Mtorc1 Also Characterize Human Metaplasiamentioning

confidence: 99%

“…In the chronic case, SPEM is equivalent to the lesion pathologists call chronic atrophic gastritis (Rugge et al, 2008). In addition, SPEM is thought to progress to (or predate) another, proliferative, pre-cancerous lesion, intestinal metaplasia (Yoshizawa et al, 2007;Correa & Piazuelo, 2012;Spechler et al, 2017) and to increase risk for progression to a cytologically atypical lesion, dysplasia, as well as to cancer itself.…”

Section: Changes In Mtorc1 Also Characterize Human Metaplasiamentioning

confidence: 99%

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Regenerative proliferation of differentiated cells by mTORC 1‐dependent paligenosis

et al. 2018

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In 1900, Adami speculated that a sequence of context-independent energetic and structural changes governed the reversion of differentiated cells to a proliferative, regenerative state. Accordingly, we show here that differentiated cells in diverse organs become proliferative via a shared program. Metaplasia-inducing injury caused both gastric chief and pancreatic acinar cells to decrease mTORC1 activity and massively upregulate lysosomes/autophagosomes; then increase damage associated metaplastic genes such as ; and finally reactivate mTORC1 and re-enter the cell cycle. Blocking mTORC1 permitted autophagy and metaplastic gene induction but blocked cell cycle re-entry at S-phase. In kidney and liver regeneration and in human gastric metaplasia, mTORC1 also correlated with proliferation. In lysosome-defective mice, both metaplasia-associated gene expression changes and mTORC1-mediated proliferation were deficient in pancreas and stomach. Our findings indicate differentiated cells become proliferative using a sequential program with intervening checkpoints: (i) differentiated cell structure degradation; (ii) metaplasia- or progenitor-associated gene induction; (iii) cell cycle re-entry. We propose this program, which we term "paligenosis", is a fundamental process, like apoptosis, available to differentiated cells to fuel regeneration following injury.

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Section: Changes In Mtorc1 Also Characterize Human Metaplasiamentioning

confidence: 99%

Section: Changes In Mtorc1 Also Characterize Human Metaplasiamentioning

confidence: 99%

Regenerative proliferation of differentiated cells by mTORC 1‐dependent paligenosis

et al. 2018

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“…Therefore, the cell of origin for the metaplastic cells becomes ambiguous and sometimes controversial. Barrett oesophagus has garnered attention in this context 57–60 . Studies in transgenic mice have revealed that the interleukin-1β (IL-1β)–IL-6 signalling cascade and Delta-like protein 1 (DLL1)-dependent Notch signalling cause Barrett oesophagus 61 .…”

Section: Cell Of Originmentioning

confidence: 99%

Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence

2017

Self Cite

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Metaplasia is the replacement of one differentiated somatic cell type with another differentiated somatic cell type in the same tissue. Typically, metaplasia is triggered by environmental stimuli, which may act in concert with the deleterious effects of microorganisms and inflammation. The cell of origin for intestinal metaplasia in the oesophagus and stomach and for pancreatic acinar–ductal metaplasia has been posited through genetic mouse models and lineage tracing but has not been identified in other types of metaplasia, such as squamous metaplasia. A hallmark of metaplasia is a change in cellular identity, and this process can be regulated by transcription factors that initiate and/or maintain cellular identity, perhaps in concert with epigenetic reprogramming. Universally, metaplasia is a precursor to low-grade dysplasia, which can culminate in high-grade dysplasia and carcinoma. Improved clinical screening for and surveillance of metaplasia might lead to better prevention or early detection of dysplasia and cancer.

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“…In summary, considerable debate continues on the cell of origin of Barrett's oesophagus, 82,83 though it is widely accepted that it is the requisite precursor lesion for the development of OAC. At least four candidate founder cells present themselves: basal cells of the squamous epithelium, stem cells of submucosal ducts, stem cells of the proximal stomach and transitional cells at the SCJ.…”

Section: Alisonmentioning

confidence: 99%

The cellular origins of cancer with particular reference to the gastrointestinal tract

Alison

2020

Int J Experimental Path

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Summary Stem cells or their closely related committed progenitor cells are the likely founder cells of most neoplasms. In the continually renewing and hierarchically organized epithelia of the oesophagus, stomach and intestine, homeostatic stem cells are located at the beginning of the cell flux, in the basal layer of the oesophagus, the isthmic region of gastric oxyntic glands and at the bottom of gastric pyloric‐antral glands and colonic crypts. The introduction of mutant oncogenes such as KrasG12D or loss of Tp53 or Apc to specific cell types expressing the likes of Lgr5 and Mist1 can be readily accomplished in genetically engineered mouse models to initiate tumorigenesis. Other origins of cancer are discussed including ‘reserve’ stem cells that may be activated by damage or through disruption of morphogen gradients along the crypt axis. In the liver and pancreas, with little cell turnover and no obvious stem cell markers, the importance of regenerative hyperplasia associated with chronic inflammation to tumour initiation is vividly apparent, though inflammatory conditions in the renewing populations are also permissive for tumour induction. In the liver, hepatocytes, biliary epithelial cells and hepatic progenitor cells are embryologically related, and all can give rise to hepatocellular carcinoma and cholangiocarcinoma. In the exocrine pancreas, both acinar and ductal cells can give rise to pancreatic ductal adenocarcinoma (PDAC), although the preceding preneoplastic states are quite different: acinar‐ductal metaplasia gives rise to pancreatic intraepithelial neoplasia culminating in PDAC, while ducts give rise to PDAC via. mucinous cell metaplasia that may have a polyclonal origin.

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A Summary of the 2016 James W. Freston Conference of the American Gastroenterological Association: Intestinal Metaplasia in the Esophagus and Stomach: Origins, Differences, Similarities and Significance

Cited by 19 publications

References 87 publications

Regenerative proliferation of differentiated cells by mTORC 1‐dependent paligenosis

Regenerative proliferation of differentiated cells by mTORC 1‐dependent paligenosis

Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence

The cellular origins of cancer with particular reference to the gastrointestinal tract

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