Linker Threonine-phosphorylated Smad2/3 Is a Biomarker of Colorectal Neoplastic Stem-like Cells that Correlates With Carcinogenesis.

Abstract

BACKGROUND/AIM:

This study analysed threonine-phosphorylated Smad2/3 (pSmad2/3L-Thr) expression and investigated whether pSmad2/3L-Thr is related to the transition from human colorectal adenoma (CRA) to carcinoma (CRC).

MATERIALS AND METHODS:

Immunofluorescent staining was performed forβ-catenin, p53, CDK4, Ki67, Sox9, aldehyde dehydrogenase (ALDH) 1, and pSmad2/3L-Thr.

RESULTS:

We analysed specimens of diffuse p53-positive CRCs arising from p53-negative CRAs. Percentage of p53, nuclear β-catenin, Ki67, CDK4, and pSmad2/3L-Thr-positive cells at the site of CRCs was significantly higher than that at the site of CRAs. At the site of normal colorectal mucosae, few epithelial cells were stained positively for pSmad2/3L-Thr. At the site of CRCs, pSmad2/3L-Thr-positive cells showed co-localization with p53, nuclear β-catenin, and ALDH1. At any site, pSmad2/3L-Thr-positive cells showed co-localization with CDK4.

CONCLUSION:

pSmad2/3L-Thr correlates with human CRC carcinogenesis, and pSmad2/3L-Thr-positive cells show human colorectal stem cell-like and cancer stem cell characteristics.

• Authors: Sachi Miyamoto, Toshiro Fukui, Shunsuke Horitani, Yuji Tanimura, Yasushi Matsumoto, Ryo Suzuki, Y U Takahashi, Masanobu Kishimoto, Takashi Tomiyama, Akiyoshi Nishio, Kazuichi Okazaki, Makoto Naganuma
• Journal: Anticancer research (Anticancer Res) Vol. 41 Issue 10 Pg. 4789-4799 (Oct 2021) ISSN: 1791-7530 [Electronic] Greece
• PMID: 34593428 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Biomarkers, Tumor
• SMAD2 protein, human
• SMAD3 protein, human
• Smad2 Protein
• Smad3 Protein
• TP53 protein, human
• Tumor Suppressor Protein p53
• Threonine

Topics

• Biomarkers, Tumor (metabolism)
• Carcinogenesis (metabolism, pathology)
• Colorectal Neoplasms (metabolism, pathology)
• Humans
• Intestinal Mucosa (metabolism, pathology)
• Neoplastic Stem Cells (metabolism, pathology)
• Phosphorylation
• Smad2 Protein (metabolism)
• Smad3 Protein (metabolism)
• Threonine (metabolism)
• Tumor Suppressor Protein p53 (metabolism)