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 Wang; Yuying Liu; Bo Huang

doi:10.15252/embj.2020106123

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 journal › Article › peer-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 language	English (US)
Article number	e106123
Pages (from-to)	e106123
Journal	The EMBO journal
Volume	40
Issue number	2
DOIs	https://doi.org/10.15252/embj.2020106123
State	Published - Jan 15 2021

Keywords

BCL9L
metastasis
microfluidic sorting
soft tumor cells
stemness

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology
Molecular Biology
General Neuroscience

Online availability

10.15252/embj.2020106123

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@article{628c12190cd54c7eac9343b89016a767,

title = "Cell softness regulates tumorigenicity and stemness of cancer cells",

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.",

keywords = "BCL9L, metastasis, microfluidic sorting, soft tumor cells, stemness",

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

note = "Funding Information: This work was supported by National Natural Science Foundation of China (81788101, 81530080, 81773062, 91942314), Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS‐I2M) 2017‐I2M‐1‐001, and 2016‐I2M‐1‐007. Funding Information: This work was supported by National Natural Science Foundation of China (81788101, 81530080, 81773062, 91942314), Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS-I2M) 2017-I2M-1-001, and 2016-I2M-1-007.",

year = "2021",

month = jan,

day = "15",

doi = "10.15252/embj.2020106123",

language = "English (US)",

volume = "40",

pages = "e106123",

journal = "The EMBO journal",

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TY - JOUR

T1 - Cell softness regulates tumorigenicity and stemness of cancer cells

AU - Lv, Jiadi

AU - Liu, Yaoping

AU - Cheng, Feiran

AU - Li, Jiping

AU - Zhou, Yabo

AU - Zhang, Tianzhen

AU - Zhou, Nannan

AU - Li, Cong

AU - Wang, Zhenfeng

AU - Ma, Longfei

AU - Liu, Mengyu

AU - Zhu, Qiang

AU - Liu, Xiaohan

AU - Tang, Ke

AU - Ma, Jingwei

AU - Zhang, Huafeng

AU - Xie, Jing

AU - Fang, Yi

AU - Zhang, Haizeng

AU - Wang, Ning

AU - Liu, Yuying

AU - Huang, Bo

N1 - Funding Information: This work was supported by National Natural Science Foundation of China (81788101, 81530080, 81773062, 91942314), Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS‐I2M) 2017‐I2M‐1‐001, and 2016‐I2M‐1‐007. Funding Information: This work was supported by National Natural Science Foundation of China (81788101, 81530080, 81773062, 91942314), Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS-I2M) 2017-I2M-1-001, and 2016-I2M-1-007.

PY - 2021/1/15

Y1 - 2021/1/15

N2 - 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.

AB - 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.

KW - BCL9L

KW - metastasis

KW - microfluidic sorting

KW - soft tumor cells

KW - stemness

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U2 - 10.15252/embj.2020106123

DO - 10.15252/embj.2020106123

M3 - Article

C2 - 33274785

SN - 0261-4189

VL - 40

SP - e106123

JO - The EMBO journal

JF - The EMBO journal

IS - 2

M1 - e106123

ER -

Cell softness regulates tumorigenicity and stemness of cancer cells

Abstract

Keywords

ASJC Scopus subject areas

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