OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway

Wei, Hongfa1,2; Li, Wenchao2,4; Zeng, Leli3; Ding, Ni3,4; Li, Kuan2; Yu, Hong2; Jiang, Fei2; Yin, Haofan2,5; Xia, Yu3; Deng, Cuncan2; Cai, Nan2; Chen, Xiancong2; Gu, Liang2; Chen, Huanjie1; Zhang, Feiran1; He, Yulong2; Li, Jia2,3; Zhang, Changhua2

2024-06-07

10.1186/s12943-024-02016-9

MOLECULAR CANCER   影响因子和分区

1476-4598

Background Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression.Methods In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM.Results Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3 beta and resulted in increased beta-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells.Conclusions OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.

SCI

英语

其他

Biochemistry & Molecular Biology ; Oncology

Biochemistry & Molecular Biology ; Oncology

WOS:001243675000002

BMC

Web of Science

1.Shantou Univ, Affiliated Hosp 1, Med Coll, Dept Gen Surg, Shantou 515041, Guangdong, Peoples R China
2.Sun Yat Sen Univ, Affiliated Hosp 7, Digest Dis Ctr, Dept Gastrointestinal Surg, Shenzhen 518107, Peoples R China
3.Sun Yat Sen Univ, Affiliated Hosp 7, Sci Res Ctr, Biobank, Shenzhen 518107, Guangdong, Peoples R China
4.Sun Yat Sen Univ, Affiliated Hosp 3, Dept Thyroid & Breast Surg, Guangzhou, Peoples R China
5.Southern Univ Sci Technol, Jinan Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp,Dept Lab Med,Clin Med Coll 2, Shenzhen, Guangdong, Peoples R China

Wei, Hongfa,Li, Wenchao,Zeng, Leli,et al. OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway[J]. MOLECULAR CANCER,2024,23(1).

Wei, Hongfa.,Li, Wenchao.,Zeng, Leli.,Ding, Ni.,Li, Kuan.,...&Zhang, Changhua.(2024).OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway.MOLECULAR CANCER,23(1).

Wei, Hongfa,et al."OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway".MOLECULAR CANCER 23.1(2024).