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Cell softness regulates tumorigenicity and stemness of cancer cells
Author(s) -
Lv Jiadi,
Liu Yaoping,
Cheng Feiran,
Li Jiping,
Zhou Yabo,
Zhang Tianzhen,
Zhou Nannan,
Li Cong,
Wang Zhenfeng,
Ma Longfei,
Liu Mengyu,
Zhu Qiang,
Liu Xiaohan,
Tang Ke,
Ma Jingwei,
Zhang Huafeng,
Xie Jing,
Fang Yi,
Zhang Haizeng,
Wang Ning,
Liu Yuying,
Huang Bo
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020106123
Subject(s) - biology , cancer research , microbiology and biotechnology , cancer cell , cell , cancer , genetics
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.