S100A11 is involved in the progression of colorectal cancer through the desmosome-catenin-TCF signaling pathway

Sep 21, 2026

Evidence indicates that high S100A11 expression correlates with multiple cancer types. It is strongly expressed in squamous cell carcinoma, mesothelioma, and pancreatic cancers, and extracellular S100A11 is linked to cancer progression. Yet most S100A11 remains intracellularly, and intracellular mechanisms in cancer cells remain insufficiently defined. This study investigates S100A11 functions in colorectal cancer cells, showing that overexpression enhances proliferation and migration, whereas knockdown suppresses these behaviors.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

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Abstract

Introduction

S100 proteins and cancer relevance

Materials and methods

In Vitro Cellular & Developmental Biology-Animal (2024) 60:1138–1149 [https://doi.org/10.1007/s1](https://doi.org/10.1007/s1) 1626-024-00930-2 S100A11 is involved in the progression of colorectal cancer through the desmosome‑catenin‑TCF signaling pathway Jin Zhou1,2 · Hitoshi Murata1 · Nahoko Tomonobu1 · Naoko Mizuta1 · AtsukoYamakawa1 · Ken‑ichi Yamamoto1 · Rie Kinoshita1 · Masakiyo Sakaguchi1 Received: 6 March 2024 / Accepted: 16 May 2024 / Published online: 6 June 2024 / Editor: Tetsuji Okamoto © The Author(s) 2024, corrected publication 2024 Abstract Compiling evidence has indicated that S100A11 expression at high levels is closely associated with various cancer species. Consistent with the results reported elsewhere, we have also revealed that S100A11 is highly expressed in squamous cell carcinoma, mesothelioma, and pancreatic cancers and plays a crucial role in cancer progression when secreted into extracellular fluid. Those studies are all focused on the extracellular role of S100A11 . However, most of S100A11 is still present within cancer cells, although the intracellular role of S100A11 in cancer cells has not been fully elucidated. Thus, we aimed to investigate S100A11 functions within cancer cells, primarily focusing on colorectal cancer cells, whose S100A11 is abundantly present in cells and still poorly studied cancer for the protein. Our efforts revealed that overexpression of S100A11 promotes proliferation and migration, and downregulation inversely dampens those cancer behaviors. To clarify how intracellular S100A11 aids cancer cell activation, we tried to identify S100A11 binding proteins, resulting in novel binding partners in the inner membrane, many of which are desmosome proteins. Our molecular approach defined that S100A11 regulates the expression level of DSG1, a component protein of desmosome, by which S100A11 activates the TCF pathway via promoting nuclear translocation of γ-catenin from the desmosome. The identified new pathway greatly helps to comprehend S100A11’s nature in colorectal cancers and others. Keywords S100A11 · Desmosome · TCF signaling · Colorectal cancer Introduction The S100 proteins are a low-molecular-weight protein of 9–14 kDa and have a Ca2+ binding EF-hands motif in their structure. Twenty types of families (S100A1-16, B, G, P, and Z) have been discovered in humans, and they function not only intracellularly but also by being secreted extracellularly (Singh and Ali 2022) . S100A11 is one of the S100 proteins aliased as S100C or Calgizzarin. S100A11 is expressed in Jin Zhou and Hitoshi Murata contributed equally. * Hitoshi Murata [murata@md.okayama-u.ac.jp](murata@md.okayama-u.ac.jp) 1 Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Kita-Ku, Okayama 700-8558, Japan 2 Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology, Shenyang, Liaoning, China various tissues, but the expression level differs depending on the tissue (Zhang et al. 2021) . It has been reported that the S100 family proteins are involved in cancer growth and metastasis (Bresnick et al. 2015), and there is a difference in the expression of the S100 proteins between normal tissue and cancer tissue. S100A11 has been reported to be upregulated in various cancers, including pancreatic and colorectal (Meding et al. 2012 ; Zhang et al. 2019 ; Wang et al. 2021 ; Zeng et al. 2022 ; Zheng et al. 2023) . We previously reported that S100A11 secreted from pancreatic cancer cells promotes the proliferation of surrounding fibroblasts and is involved in cancer progression (Takamatsu et al. 2019) . On the other hand, most of S100A11 is still present within cancer cells; however, the intracellular role of S100A11 in cancer cells has not been fully elucidated. Therefore, in this study, we aimed to clarify the unidentified role o

FAQs

What role does S100A11 play in colorectal cancer cells according to the study?

S100A11 overexpression promotes cancer cell proliferation and migration, while downregulation dampens these behaviors in colorectal cancer cells.

How does intracellular S100A11 activate the TCF pathway?

Intracellular S100A11 regulates DSG1 (a desmosome component) expression and promotes nuclear translocation of γ-catenin from the desmosome, thereby activating the TCF pathway.

What new S100A11 binding partners were identified?

The study identified desmosome-related proteins as novel S100A11-interacting partners, including desmoplakin, desmoglein-1 (DSG1), plakoglobin (γ-catenin), and corneodesmosin.

Sep 21, 2026

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