Dataset Information

PECAM-1 drives β-catenin-mediated EndMT via internalization in colon cancer with diabetes mellitus.

ABSTRACT:

Background

Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression, although the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives β-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer.

Methods

The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray analysis. The effect of DM on colon cancer was determined in clinical patients and animal models. Furthermore, EndMT, PECAM-1 and Akt/GSK-3β/β-catenin signaling were analyzed under high glucose (HG) and human colon cancer cell (HCCC) supernatant (SN) or coculture conditions by western and immunofluorescence tests.

Results

DM promoted the progression and EndMT occurrence of colon cancer (CC). Regarding the mechanism, DM induced PECAM-1 defection from the cytomembrane, internalization and subsequent accumulation around the cell nucleus in endothelial cells, which promoted β-catenin entry into the nucleus, leading to EndMT occurrence in CC with DM. Additionally, Akt/GSK-3β signaling was enhanced to inhibit the degradation of β-catenin, which regulates the process of EndMT.

Conclusions

PECAM-1 defects and/or internalization are key events for β-catenin-mediated EndMT, which is significantly boosted by enhanced Akt/GSK-3β signaling in the DM-associated TME. This contributes to the mechanism by which DM promotes the carcinogenesis and progression of CC. Video Abstract.

SUBMITTER: Wu Q

PROVIDER: S-EPMC10426208 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

PECAM-1 drives β-catenin-mediated EndMT via internalization in colon cancer with diabetes mellitus.

Wu Qing Q Du Xingxing X Cheng Jianing J Qi Xiuying X Liu Huan H Lv Xiaohong X Gong Xieyang X Shao Changxin C Wang Muhong M Yue Luxiao L Yang Xin X Li Shiyu S Zhang Yafang Y Li Xuemei X Yang Huike H

Cell communication and signaling : CCS 20230814 1

<h4>Background</h4>Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression, although the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives β-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer.<h4>Methods</h4>The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray ...[more]

PMID: 37580771

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Dataset Information

PECAM-1 drives β-catenin-mediated EndMT via internalization in colon cancer with diabetes mellitus.

Background

Methods

Results

Conclusions

Publications

PECAM-1 drives β-catenin-mediated EndMT via internalization in colon cancer with diabetes mellitus.

Similar Datasets

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