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

  • Research (Wash D C). 2023 Sep 21:6:0224. doi: 10.34133/research.0224.
Xi Chen  1  2  3 ,  Zichen Xu  4  3 ,  Kai Tang  3 ,  Guanshuo Hu  1  2  3 ,  Pengyu Du  3 ,  Junfang Wang  3 ,  Cunyu Zhang  2  3 ,  Ying Xin  3 ,  Keming Li  3 ,  Qiantang Zhang  4 ,  Jianjun Hu  5 ,  Zhuxue Zhang  5 ,  Mo Yang  3 ,  Guixue Wang  4 ,  Youhua Tan  1  2  3
Affiliations
  • 1. The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518057, China.
  • 2. Research Institute of Smart Ageing, The Hong Kong Polytechnic University, Hong Kong, China.
  • 3. Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, China.
  • 4. Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China.
  • 5. Department of Pathology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, 550002, China.
PMID: 37746658 DOI: 10.34133/research.0224
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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