Emerging role of spasmolytic polypeptide-expressing metaplasia in gastric cancer DOI Open Access
Qiange Ye, Yanmei Zhu, Yuxiang Ma

и другие.

Journal of Gastrointestinal Oncology, Год журнала: 2024, Номер 15(6), С. 2673 - 2683

Опубликована: Дек. 1, 2024

Gastric cancer (GC) ranks among the top five most diagnosed cancers globally, with particularly high incidence and mortality rates observed in Asian regions. Despite certain advancements achieved through early screening treatment strategies many countries, GC continues to pose a significant public health challenge. Approximately 20% of patients infected Helicobacter pylori develop precancerous lesions, which metaplasia is critical. Except for intestinal (IM), characterized by goblet cells appearing stomach glands, one type mucous cell metaplasia, spasmolytic polypeptide-expressing (SPEM), has attracted much attention. SPEM represents specific epithelial alteration within gastric mucosa, expressing trefoil factor 2 (TFF2) basal resembling deep antral gland cells. It primarily arises from transdifferentiation mature chief cells, neck (MNCs), or isthmus stem commonly regarded as precursor lesion development inflammation subsequent carcinogenesis. The formation intricately associated chronic inflammation, infection, various other environmental genetic factors. Recently, profound exploration biological molecular mechanisms underlying SPEM, deeper understanding its role initiation progression emerged. This review summarizes role, mechanisms, clinical significance onset GC.

Язык: Английский

Origins of cancer: ain’t it just mature cells misbehaving? DOI

Charles J. Cho,

Jeffrey W. Brown, Jason C. Mills

и другие.

The EMBO Journal, Год журнала: 2024, Номер 43(13), С. 2530 - 2551

Опубликована: Май 21, 2024

Язык: Английский

Процитировано

10
Integrative Investigation on the Mechanisms of Modified Zuojin Pill (SQQT) in Ameliorating Gastric Metaplasia DOI
Xuefei Yang, Jiaqi Zhang, Jing Ma

и другие.

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119643 - 119643

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Autophagy-Dependent Regulation of YAP1 by STK38 Governs Recruitment of Differentiated Cells as Progenitor Cells During Regeneration DOI
Yongji Zeng, Yang‐Zhe Huang, Qing Kay Li

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Abstract Paligenosis is a conserved cellular plasticity program that allows mature cells to reenter the cell cycle in response tissue injury. progresses via three stages: autodegradation (with dramatic increase autophagy and lysosomes), induction of metaplastic or fetal-like genes, entry. Hippo signaling, particularly downstream effector YAP1, regulates plasticity, but its role paligenosis has not been studied. Here we first examine digestive-enzyme-secreting chief mouse stomach. We identify Serine/Threonine Kinase 38 (STK38) as non-canonical YAP1 kinase phosphorylated deactivated uninjured cells. During paligenosis, STK38 was degraded by stage 1, dephosphorylating activating YAP1. activation necessary sufficient for converts into metaplastic, proliferating progenitors. Additionally, show STK38, like canonical kinases, interact with NF2. also observed same pattern autophagic destruction other tissues types, suggesting universal logic model how massive activated differentiated during damage can consequently activate effectors induce regeneration.

Язык: Английский

Процитировано

0
The protective role of DDIT4 in Helicobacter pylori-induced gastric metaplasia through metabolic regulation of ferroptosis DOI Creative Commons
Huan Wang, Xinbo Xu, Yaobin Ouyang

и другие.

Cellular and Molecular Gastroenterology and Hepatology, Год журнала: 2024, Номер unknown, С. 101448 - 101448

Опубликована: Дек. 1, 2024

Helicobacter pylori (H. pylori) infection is a significant factor leading to gastric atrophy, metaplasia and cancer development. Here, we investigated the role of stress response gene DDIT4 in pathogenesis H. infection. Cell lines, transgenic mice, human tissue samples were implemented. Proteomics performed on Ddit4+/+ Ddit4-/- mice infected with strain PMSS1. C57BL/6 administered tamoxifen induce metaplasia. Stomach tissues analyzed for histopathologic features, reactive oxygen species, Fe2+, lipid peroxidation, expression DDIT4, ferroptosis-related proteins. was upregulated at 6 hours but significantly decreased 24 epithelial cells. Gastric downregulated INS-GAS 4 months post Notably, led more severe lesion Ddit4-knockout mice. The proteomic profiling revealed an increase ferroptosis Ddit4-deficient compared wild-type Mechanistically, knockout promoted pylori-induced through accumulation peroxides ROS levels, alterations proteins such as GPX4, ALOX15, HMOX1. Overexpression counteracted stem cell marker CD44V9 modulation ferroptosis. Similarly, another mouse model treated tamoxifen, well GIM tissues, observed loss induction Our results indicate that serves protective against by metabolic resistance

Язык: Английский

Процитировано

1
Cathartocytosis: How Cells Jettison Unwanted Material as They Reprogram DOI Open Access
Jeffrey W. Brown,

Xiaobo Lin,

Gabriel Anthony Nicolazzi

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 13, 2024

ABSTRACT Injury can cause differentiated cells to undergo massive reprogramming become proliferative repair tissue via a cellular program called paligenosis. Gastric digestive-enzyme-secreting chief use paligenosis reprogram into progenitor-like Spasmolytic-Polypeptide Expressing Metaplasia (SPEM) cells. Stage 1 of is the downscaling mature cell architecture process involving lysosomes. Here, we noticed that sulfated glycoproteins were not only digested during but also excreted gland lumen. Various genetic and pharmacological approaches showed endoplasmic reticulum membranes secretory granule cargo proceeded in parallel with, was mechanistically independent autophagy. 3-dimensional light electron-microscopy demonstrated excretion occurred unique, complex, multi-chambered invaginations apical plasma membrane. As this lysosome-independent cleansing does seem have been priorly described, termed it “cathartocytosis”. Cathartocytosis allows rapidly eject excess material without waiting for autophagic lysosomal digestion. We speculate ejection would aid might help bind flush pathogens away from tissue.

Язык: Английский

Процитировано

0
H. Pylori‐Facilitated TERT/Wnt/β‐Catenin Triggers Spasmolytic Polypeptide‐Expressing Metaplasia and Oxyntic Atrophy DOI Creative Commons
Lijiao He, Xiao Zhang, Shengwei Zhang

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 25, 2024

Abstract Persistent H. pylori infection triggers the repair program of mucosa, such as spasmolytic polypeptide‐expressing metaplasia (SPEM). However, mechanism underlying initiation SPEM in gastric tissues by remains unclear. Here, an increase telomerase reverse transcriptase (TERT) protein expression is observed chief cells upon with cagA ‐positive . Tert knockout significantly ameliorated ‐induced and single‐cell RNA sequencing demonstrated that Wnt/β‐Catenin pathway suppressed knockout. Mechanism study revealed CagA elevated TERT abundance disrupting interaction between its novel E3 ligase, SYVN1. Interestingly, Nitazoxanide effectively relieved via inhibition signaling vivo. This results clarified which activated TERT/Wnt/β‐Catenin pathway, thus promoting dedifferentiation occurrence mucosa. highlights a molecular basis for targeting CagA‐activated Wnt treatment precancerous lesions.

Язык: Английский

Процитировано

0
Emerging role of spasmolytic polypeptide-expressing metaplasia in gastric cancer DOI Open Access
Qiange Ye, Yanmei Zhu, Yuxiang Ma

и другие.

Journal of Gastrointestinal Oncology, Год журнала: 2024, Номер 15(6), С. 2673 - 2683

Опубликована: Дек. 1, 2024

Gastric cancer (GC) ranks among the top five most diagnosed cancers globally, with particularly high incidence and mortality rates observed in Asian regions. Despite certain advancements achieved through early screening treatment strategies many countries, GC continues to pose a significant public health challenge. Approximately 20% of patients infected Helicobacter pylori develop precancerous lesions, which metaplasia is critical. Except for intestinal (IM), characterized by goblet cells appearing stomach glands, one type mucous cell metaplasia, spasmolytic polypeptide-expressing (SPEM), has attracted much attention. SPEM represents specific epithelial alteration within gastric mucosa, expressing trefoil factor 2 (TFF2) basal resembling deep antral gland cells. It primarily arises from transdifferentiation mature chief cells, neck (MNCs), or isthmus stem commonly regarded as precursor lesion development inflammation subsequent carcinogenesis. The formation intricately associated chronic inflammation, infection, various other environmental genetic factors. Recently, profound exploration biological molecular mechanisms underlying SPEM, deeper understanding its role initiation progression emerged. This review summarizes role, mechanisms, clinical significance onset GC.

Язык: Английский

Процитировано

0