RXRα-enriched cancer stem cell-like properties triggered by CDDP in head and neck squamous cell carcinoma (HNSCC)

Abstract

Retinoid X receptor-α (RXRα) is a kind of nuclear receptor and is a target of cancer prevention and treatment in various types of cancers. Cancer stem cells (CSCs) are regarded as the main cause of carcinoma metastasis, tumor recurrence and chemotherapy resistance. So far, the mechanism how RXRα regulates CSCs remains unknown. In the present study, we found that RXRα was upregulated in head and neck squamous cell carcinoma (HNSCC) tissues and the enriched HNSCC CSCs. Overexpression of RXRα was able to expand the CSC-like properties in HNSCC cells, whereas knockdown of RXRα could repress the stemness respectively. Meanwhile, low doses of cisplatin (CDDP) increased the CSC-like properties and RXRα expression in HNSCC cells. Also, Wnt signaling pathway played a significant role in CDDP-induced CSCs. Simultaneously, curcumin, a plant polyphenol, which is an effective anticancer compound, exhibited an inhibitory effect in the HNSCC CSCs induced by CDDP in vitro and in vivo. Via inhibition of RXRα, curcumin suppressed CSC-like phenotypes induced by CDDP. These findings may suggest a novel mechanism for HNSCC treatment.