Dynamic Expansion of Gastric Mucosal Doublecortin-Like Kinase 1–Expressing Cells in Response to Parietal Cell Loss Is Regulated by Gastrin

Choi, Eunyoung; Petersen, Christine; Lapierre, Lynne A.; Williams, Janice A.; Weis, Victoria G.; Goldenring, James R.; Nam, Ki Taek

doi:10.1016/j.ajpath.2015.04.009

Cited by 25 publications

(32 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results reported as a part of a previous larger study 32 indicate that Lrig1-expressing cells are able to contribute to formation of Tuft cells, suggesting their role in tissue maintenance. While this manuscript was under consideration, another study by Choi et al .…”

Section: Discussionmentioning

confidence: 72%

Lrig1 marks a population of gastric epithelial cells capable of long-term tissue maintenance and growth in vitro

Schweiger

Clement

Page

et al. 2018

Sci Rep

View full text Add to dashboard Cite

The processes involved in renewal of the epithelium that lines the mouse stomach remain unclear. Apart from the cells in the isthmus, several other populations located deeper in the gastric glands have been suggested to contribute to the maintenance of the gastric epithelium. Here, we reveal that Lrig1 is expressed in the basal layer of the forestomach and the lower part of glands in the corpus and pylorus. In the glandular epithelium of the stomach, Lrig1 marks a heterogeneous population comprising mainly non-proliferative cells. Yet, fate-mapping experiments using a knock-in mouse line expressing Cre specifically in Lrig1+ cells demonstrate that these cells are able to contribute to the long-term maintenance of the gastric epithelium. Moreover, when cultured in vitro, cells expressing high level of Lrig1 have much higher organoid forming potential than the corresponding cellular populations expressing lower levels of Lrig1. Taken together, these observations show that Lrig1 is expressed primarily by differentiated cells, but that these cells can be recruited to contribute to the maintenance of the gastric epithelium. This confirms previous observations that cells located in the lower segments of gastric glands can participate in tissue replenishment.

show abstract

Section: Discussionmentioning

confidence: 72%

Lrig1 marks a population of gastric epithelial cells capable of long-term tissue maintenance and growth in vitro

Schweiger

Clement

Page

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…DCLK1 is overexpressed in many cancers, including colon, pancreas, liver, kidney [ 11 ], and esophageal cancer [ 9 , 12 – 15 ]. Studies from us and others supported that DCLK1 expression is critical for cancer growth, EMT, metastasis, and cancer cell self-renewal [ 9 , 14 , 16 – 18 ]. The functional interdependence between EMT-associated transcription factors and enhanced self-renewal highlights the common mechanism involved in their regulation.…”

Section: Introductionmentioning

confidence: 99%

Regulatory Roles of Dclk1 in Epithelial Mesenchymal Transition and Cancer Stem Cells

Chandrakesan¹,

Panneerselvam

et al. 2016

J Carcinog Mutagen

View full text Add to dashboard Cite

The identification of functionally relevant subpopulations of therapy-resistant cancer cells is a challenge. These cells, intrinsically resistant to conventional therapy, can cause recurrence. Evidence has suggested that therapy-resistant cancer cells are likely epithelial–mesenchymal transition (EMT) cells and/or stem-like cells called cancer stem cells (CSCs). EMT, a normal embryological process that converts epithelial cells into mesenchymal cells, is frequently activated during cancer development and progression. CSCs are a small subpopulation of cancer cells within a tumor mass that have the ability to self-renew and maintain tumor-initiating capacity by giving rise to heterogeneous lineages of cancer cells that comprise the whole tumor. Although the origin of CSCs and EMT cells remains to be fully explored, a growing body of evidence has indicated that the biology of EMT and CSCs is strongly linked. Doublecortin-like kinase 1 (DCLK1), a cancer stem cell marker, is functionally involved in maintaining cancer stemness and the process of EMT important for cancer initiation, cancer metastasis, and secondary tumor formation. Therefore, targeting these cells may provide new strategies to overcome tumor heterogeneity, therapeutic resistance, and cancer relapse. In this review, we will provide a potential mechanistic link between EMT induction and the emergence of CSCs for the origin and progression of cancer. We will highlight the functional activity of DCLK1 in supporting EMT and cancer cell self-renewal, which will lead us to a better understanding of DCLK1 expression in cancer development and progression, and help us to develop targeted therapies for effective cancer treatment.

show abstract

“…It also has been reported that DCLK1-expressing cells are expanded in an ulcer, 12 as well as in response to loss of parietal cells. 37 We observed that DCLK1 was up-regulated significantly in the regenerated epithelium ( Figures 3 A–C and 5 C ). Immunofluorescence showed that DCLK1-positive cells also expressed SOX9, whereas a large number of SOX9-positive cells did not co-express with DCLK1 ( Figure 5 D ).…”

Section: Resultsmentioning

confidence: 71%

“… 12 , 19 , 24 , 38 It has been reported that DCLK1 is up-regulated in response to a loss of parietal cells and metaplasia, including ulcerated tissue, but its functional role remains unknown. 12 , 37 Because DCLK1-positive cells were not positive for Ki67, they likely do not function as stem/progenitor cells. In the ulcer, UEA-1–positive cells expanded deep into the gland along with GSII- or TFF2-positive cells.…”

Section: Discussionmentioning

confidence: 99%

Epithelial Regeneration After Gastric Ulceration Causes Prolonged Cell-Type Alterations

Aihara

Matthis

Karns

et al. 2016

Cellular and Molecular Gastroenterology and Hepatology

View full text Add to dashboard Cite

Background & Aim The peptic ulcer heals through a complex process, although the ulcer relapse often occurs several years later after healing. Our hypothesis is that even after visual evidence of healing of gastric ulceration, the regenerated epithelium is aberrant for an extended interval, increasing susceptibility of the regenerated epithelium to damage and further diseases. Methods Gastric ulcers were induced in mice by serosal topical application of acetic acid. Results Gastric ulcers induced by acetic acid visually healed within 30 days. However, regenerated epithelial architecture was poor. The gene profile of regenerated tissue was abnormal, indicating increased stem/progenitor cells, deficient differentiated gastric cell types, and deranged cell homeostasis. Despite upregulation of PDX1 in the regenerated epithelium, no mature antral cell type was observed. Four months after healing, the regenerated epithelium lacks parietal cells, TFF2 and SOX9 remain upregulated deep in the gastric gland, and the Na/H exchanger 2 (a TFF2 effector in gastric healing) remains downregulated. Gastric ulcer healing was strongly delayed in TFF2 knockout mice, and re-epithelialization was accompanied with mucous metaplasia. Following H. pylori inoculum 30 days after ulceration, we observed that the gastric ulcer selectively relapses at the same site where it was originally induced. Follow up at 8 months showed that the relapsed ulcer was not healed in H. pylori infected tissues. Conclusion These findings reveal that this macroscopically regenerated epithelium has prolonged abnormal cell distribution and is differentially susceptible to subsequent damage by H. pylori.

show abstract

Dynamic Expansion of Gastric Mucosal Doublecortin-Like Kinase 1–Expressing Cells in Response to Parietal Cell Loss Is Regulated by Gastrin

Cited by 25 publications

References 38 publications

Lrig1 marks a population of gastric epithelial cells capable of long-term tissue maintenance and growth in vitro

Lrig1 marks a population of gastric epithelial cells capable of long-term tissue maintenance and growth in vitro

Regulatory Roles of Dclk1 in Epithelial Mesenchymal Transition and Cancer Stem Cells

Epithelial Regeneration After Gastric Ulceration Causes Prolonged Cell-Type Alterations

Contact Info

Product

Resources

About