STAT3 mediates resistance to anoikis and promotes invasiveness of nasopharyngeal cancer cells

Chien Hung Lin*, Ming Chang Chiang, Yann Jang Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Nasopharyngeal carcinoma (NPC), a tumor arising from the epithelial cells of the nasopharynx, is endemic in Southeast Asia and Taiwan. The prognosis of NPC patients with local recurrence and metastasis is poor. Resistance to anoikis is a primary characteristic of tumor cells that metastasize. However, the mechanism through which NPC cells resist anoikis and are able to metastasize has not been fully elucidated. In the present study, the acquisition of anoikis resistance was analyzed in the TW01 and TW06 human NPC cell lines growing under anchorage-independent conditions. A considerable number of TW01 and TW06 cells was found to be resistant to anoikis and exhibited a higher capability of migration and invasion. These anoikis-resistant NPC cells exhibited significantly increased expression of signal transducer and activation of transcription 3 (Stat 3) compared with adherent cells. Furthermore, blockade of STAT3 expression by STAT3 inhibitors or STAT3 silencing significant increased anoikis in anoikis-resistant NPC cells. Moreover, silencing STAT3 not only reduced the capacity of NPC cells to resist anoikis, but also reversed their invasive properties. The expression of epithelial-to-mesenchymal transition-related proteins and CD44 was also significantly decreased following STAT3 knockdown. The results of the present study established that STAT3 mediates anoikis resistance, with enhanced cell migration and invasion of NPC cells, and that activation of STAT3 may increase metastatic capacity, indicating the crucial role of STAT3 in conferring anoikis resistance and enhanced invasive properties to NPC cells.

Original languageEnglish
Pages (from-to)1549-1556
Number of pages8
JournalInternational Journal of Molecular Medicine
Volume40
Issue number5
DOIs
StatePublished - Nov 2017

Keywords

  • Anoikis
  • Nasopharyngeal carcinoma
  • Neoplasm invasiveness
  • Signal transducer and activator of transcription 3

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