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

Cancers (Basel). 2021 Apr 12;13(8):1833. doi: 10.3390/cancers13081833.

Authors

Tsai-Tsen Liao^{1

2}, Wei-Chung Cheng^{3

4}, Chih-Yung Yang^{5

6}, Yin-Quan Chen⁷, Shu-Han Su⁸, Tzu-Yu Yeh⁸, Hsin-Yi Lan^{1

9

10}, Chih-Chan Lee⁹, Hung-Hsin Lin^{11

12}, Chun-Chi Lin^{12

13}, Ruey-Hwa Lu¹⁴, Arthur Er-Terg Chiou¹⁵, Jeng-Kai Jiang^{12

13}, Wei-Lun Hwang^{7

9

10}

Affiliations

¹ Graduate Institute of Medical Science, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
² Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan.
³ Ph.D. Program for Cancer Molecular Biology and Drug Discovery, China Medical University, Taichung 406, Taiwan.
⁴ Research Center for Cancer Biology, China Medical University, Taichung 406, Taiwan.
⁵ Department of Education and Research, Taipei City Hospital, Taipei 106, Taiwan.
⁶ General Education Center, University of Taipei, Taipei 100, Taiwan.
⁷ Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
⁸ Institution of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan.
⁹ Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
¹⁰ Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 112, Taiwan.
¹¹ Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
¹² Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan.
¹³ School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
¹⁴ Department of Surgery, Zhongxing Branch, Taipei City Hospital, Taipei 106, Taiwan.
¹⁵ Institute of Biophotonics, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.

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.

Abstract

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