The microrna-210-stathmin1 axis decreases cell stiffness to facilitate the invasiveness of colorectal cancer stem cells

Tsai Tsen Liao; Wei Chung Cheng; Chih Yung Yang; Yin Quan Chen; Shu Han Su; Tzu Yu Yeh; Hsin Yi Lan; Chih Chan Lee; Hung Hsin Lin; Chun Chi Lin; Ruey Hwa Lu; Arthur Er Terg Chiou; Jeng Kai Jiang; Wei Lun Hwang

doi:10.3390/cancers13081833

The microrna-210-stathmin1 axis decreases cell stiffness to facilitate the invasiveness of colorectal cancer stem cells

Tsai Tsen Liao, Wei Chung Cheng, Chih Yung Yang, Yin Quan Chen, Shu Han Su, Tzu Yu Yeh, Hsin Yi Lan, Chih Chan Lee, Hung Hsin Lin, Chun Chi Lin, Ruey Hwa Lu, Arthur Er Terg Chiou, Jeng Kai Jiang^*, Wei Lun Hwang

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

Original language	English
Article number	1833
Journal	Cancers
Volume	13
Issue number	8
DOIs	https://doi.org/10.3390/cancers13081833
State	Published - 2 Apr 2021

Keywords

Cancer stem cells
Colon cancer
Deformability
MicroRNAs

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers13081833

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Liao, T. T., Cheng, W. C., Yang, C. Y., Chen, Y. Q., Su, S. H., Yeh, T. Y., Lan, H. Y., Lee, C. C., Lin, H. H., Lin, C. C., Lu, R. H., Chiou, A. E. T., Jiang, J. K., & Hwang, W. L. (2021). The microrna-210-stathmin1 axis decreases cell stiffness to facilitate the invasiveness of colorectal cancer stem cells. Cancers, 13(8), Article 1833. https://doi.org/10.3390/cancers13081833

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title = "The microrna-210-stathmin1 axis decreases cell stiffness to facilitate the invasiveness of colorectal cancer stem cells",

abstract = "Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.",

keywords = "Cancer stem cells, Colon cancer, Deformability, MicroRNAs",

author = "Liao, {Tsai Tsen} and Cheng, {Wei Chung} and Yang, {Chih Yung} and Chen, {Yin Quan} and Su, {Shu Han} and Yeh, {Tzu Yu} and Lan, {Hsin Yi} and Lee, {Chih Chan} and Lin, {Hung Hsin} and Lin, {Chun Chi} and Lu, {Ruey Hwa} and Chiou, {Arthur Er Terg} and Jiang, {Jeng Kai} and Hwang, {Wei Lun}",

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AU - Liao, Tsai Tsen

AU - Cheng, Wei Chung

AU - Yang, Chih Yung

AU - Chen, Yin Quan

AU - Su, Shu Han

AU - Yeh, Tzu Yu

AU - Lan, Hsin Yi

AU - Lee, Chih Chan

AU - Lin, Hung Hsin

AU - Lin, Chun Chi

AU - Lu, Ruey Hwa

AU - Chiou, Arthur Er Terg

AU - Jiang, Jeng Kai

AU - Hwang, Wei Lun

PY - 2021/4/2

Y1 - 2021/4/2

N2 - Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

AB - Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

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KW - Colon cancer

KW - Deformability

KW - MicroRNAs

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The microrna-210-stathmin1 axis decreases cell stiffness to facilitate the invasiveness of colorectal cancer stem cells

Abstract

Keywords

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