Cell softness regulates tumorigenicity and stemness of cancer cells

Jiadi Lv, Yaoping Liu, Feiran Cheng, Jiping Li, Yabo Zhou, Tianzhen Zhang, Nannan Zhou, Cong Li, Zhenfeng Wang, Longfei Ma, Mengyu Liu, Qiang Zhu, Xiaohan Liu, Ke Tang, Jingwei Ma, Huafeng Zhang, Jing Xie, Yi Fang, Haizeng Zhang, Ning WangYuying Liu, Bo Huang

Research output: Contribution to journalArticlepeer-review

Abstract

Identifying and sorting highly tumorigenic and metastatic tumor cells from a heterogeneous cell population is a daunting challenge. Here, we show that microfluidic devices can be used to sort marker-based heterogeneous cancer stem cells (CSC) into mechanically stiff and soft subpopulations. The isolated soft tumor cells (< 400 Pa) but not the stiff ones (> 700 Pa) can form a tumor in immunocompetent mice with 100 cells per inoculation. Notably, only the soft, but not the stiff cells, isolated from CD133+ , ALDH+ , or side population CSCs, are able to form a tumor with only 100 cells in NOD-SCID or immunocompetent mice. The Wnt signaling protein BCL9L is upregulated in soft tumor cells and regulates their stemness and tumorigenicity. Clinically, BCL9L expression is correlated with a worse prognosis. Our findings suggest that the intrinsic softness is a unique marker of highly tumorigenic and metastatic tumor cells.

Original languageEnglish (US)
Article numbere106123
Pages (from-to)e106123
JournalThe EMBO journal
Volume40
Issue number2
DOIs
StatePublished - Jan 15 2021

Keywords

  • BCL9L
  • metastasis
  • microfluidic sorting
  • soft tumor cells
  • stemness

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Molecular Biology
  • Neuroscience(all)

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