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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article number1833
JournalCancers
Volume13
Issue number8
DOIs
Publication statusPublished - Apr 2 2021

Keywords

  • Cancer stem cells
  • Colon cancer
  • Deformability
  • MicroRNAs

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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