JOURNAL ARTICLE

SNAIL induces epithelial-to-mesenchymal transition and cancer stem cell-like properties in aldehyde dehydroghenase-negative thyroid cancer cells

Kazuaki Yasui, Mika Shimamura, Norisato Mitsutake, Yuji Nagayama
Thyroid: Official Journal of the American Thyroid Association 2013, 23 (8): 989-96
23432420

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is thought to play a critical role in the invasion and metastasis of cancer and to be associated with cancer stem cell (CSC) properties. It is not clear if there is a link between EMT and CSCs in thyroid cancers. We therefore investigated the CSC properties of thyroid cancers that underwent EMT.

METHOD: To induce EMT (spindle-like cell morphology, loss and acquisition of expression of an epithelial marker E-cadherin and a mesenchymal marker vimentin respectively) in an epithelial-type thyroid cancer cell line ACT-1, we used transforming growth factor-β (TGF-β), BRAF(V600E), and/or Snail homolog 1 (SNAI1, also known as SNAIL). CSC properties were analyzed with assays for cell proliferation, chemosensitivity, in vitro and in vivo tumor formation ability, cell surface antigens, and intracellular aldehyde dehydrogenase (ALDH; a known CSC marker) activities.

RESULTS: EMT was induced most efficiently by SNAIL (ACT-SNAIL cells), whereas TGF-β and BRAF(V600E) were less efficient. ACT-SNAIL cells showed slightly but significantly enhanced tumor formation ability in an in vitro sphere assay (approximately 3-fold) but not an in vivo subcutaneous tumor growth assay, and showed comparable chemosensitivity compared with the parental ACT-1 cells. However, of interest, although the in vitro sphere-formation ability of ALDH(+) cells was almost unchanged after SNAIL induction, SNAIL overexpression induced much higher (approximately 14-fold) spheres in ALDH(-) cells. Thus, ALDH was no longer a CSC marker in ACT-SNAIL cells.

CONCLUSIONS: All these data indicate that EMT confers CSC properties in ALDH(-) cells and appears to influence the ability of ALDH to enrich CSCs.

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