@article{816ea47a7d604c29b866139e2500f54a,
title = "MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells",
abstract = "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.",
author = "Hwang, {Wei Lun} and Jiang, {Jeng Kae} and Yang, {Shung Haur} and Huang, {Tse Shun} and Lan, {Hsin Yi} and Teng, {Hao Wei} and Yang, {Chih Yung} and Tsai, {Ya Ping} and Lin, {Chi Hung} and Wang, {Hsei Wei} and Yang, {Muh Hwa}",
note = "Funding Information: We thank the National Yang-Ming University-VGH Genome Research Center for technical support. We thank K.-J. Wu (National Yang-Ming University) for providing the wild-type and mutant β-catenin constructs. This work was supported by the National Science Council (NSC102-2321-B-010-006 and 102-2314-B-010-044 to M-H.Y.; 101-2321-B-010-011, 102-2314-B-010-045, 101-2320-B-010-059-MY3 and 101-2627-B-010-003 to H-W.W.; 100-2321-B-075-004 and 101-2321-B-075-001 to J-K.J.), the National Health Research Institutes (NHRI-EX102-10037BI to M-H.Y. and NHRI-EX102-10254SI to H-W.W.), Taipei City Hospital (10201-62-070 to H-W.W.), a grant from the Ministry of Education, Aim for the Top University Plan (to MH.Y. and H-W.W.), a grant from the Department of Health, Center of Excellence for Cancer Research (DOH102-TD-C-111-007 to M-H.Y. and H-W.W.), and the UST-UCSD International Center for Excellence in Advanced Bioengineering sponsored by the Taiwan NSC I-RiCE (NSC101-2911-I-009-101 to H-W.W.).",
year = "2014",
month = mar,
doi = "10.1038/ncb2910",
language = "English",
volume = "16",
pages = "268--280",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "3",
}
