MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells

Wei Lun Hwang, Jeng Kae Jiang, Shung Haur Yang, Tse Shun Huang, Hsin Yi Lan, Hao Wei Teng, Chih Yung Yang, Ya Ping Tsai, Chi Hung Lin, Hsei Wei Wang*, Muh Hwa Yang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

192 Scopus citations


Asymmetrical cell division (ACD) maintains the proper number of stem cells to ensure self-renewal. In cancer cells, the deregulation of ACD disrupts the homeostasis of the stem cell pool and promotes tumour growth. However, this mechanism is unclear. Here, we show a reduction of ACD in spheroid-derived colorectal cancer stem cells (CRCSCs) compared with differentiated cancer cells. The epithelial-mesenchymal transition (EMT) inducer Snail is responsible for the ACD-to-symmetrical cell division (SCD) switch in CRCSCs. Mechanistically, Snail induces the expression of microRNA-146a (miR-146a) through the β-catenin-TCF4 complex. miR-146a targets Numb to stabilize β-catenin, which forms a feedback circuit to maintain Wnt activity and directs SCD. Interference with the Snail-miR-146a-β-catenin loop by inhibiting the MEK or Wnt activity reduces the symmetrical division of CRCSCs and attenuates tumorigenicity. In colorectal cancer patients, the Snail HighNumbLow profile is correlated with cetuximab resistance and a poorer prognosis. This study elucidates a unique mechanism of EMT-induced CRCSC expansion.

Original languageEnglish
Pages (from-to)268-280
Number of pages13
JournalNature Cell Biology
Issue number3
StatePublished - Mar 2014


Dive into the research topics of 'MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells'. Together they form a unique fingerprint.

Cite this