The Mechanics of Tumor Cells Dictate Malignancy Via Cytoskeleton-Mediated APC/Wnt/β-Catenin Signaling

Overview

Journal Research (Wash D C)

Specialty Biology

Date 2023 Sep 25

PMID 37746658

Authors

Xi Chen

Zichen Xu

Kai Tang

Guanshuo Hu

Pengyu Du

Junfang Wang

Cunyu Zhang

Ying Xin

Keming Li

Qiantang Zhang

Jianjun Hu

Zhuxue Zhang

Mo Yang

Guixue Wang

Youhua Tan

Affiliations

Soon will be listed here.

Abstract

Tumor cells progressively remodel cytoskeletal structures and reduce cellular stiffness during tumor progression, implicating the correlation between cell mechanics and malignancy. However, the roles of tumor cell cytoskeleton and the mechanics in tumor progression remain incompletely understood. We report that softening/stiffening tumor cells by targeting actomyosin promotes/suppresses self-renewal in vitro and tumorigenic potential in vivo. Weakening/strengthening actin cytoskeleton impairs/reinforces the interaction between adenomatous polyposis coli (APC) and β-catenin, which facilitates β-catenin nuclear/cytoplasmic localization. Nuclear β-catenin binds to the promoter of Oct4, which enhances its transcription that is crucial in sustaining self-renewal and malignancy. These results demonstrate that the mechanics of tumor cells dictate self-renewal through cytoskeleton-APC-Wnt/β-catenin-Oct4 signaling, which are correlated with tumor differentiation and patient survival. This study unveils an uncovered regulatory role of cell mechanics in self-renewal and malignancy, and identifies tumor cell mechanics as a hallmark not only for cancer diagnosis but also for mechanotargeting.

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