Blocking autophagy flux promotes interferon-alpha-mediated apoptosis in head and neck squamous cell carcinoma

Wenyi Yang, Chunlan Jiang, Weiya Xia, Houyu Ju, Shufang Jin, Shuli Liu, Liming Zhang, Guoxin Ren, Hailong Ma, Min Ruan, Jingzhou Hu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Despite multiple antitumor activities, interferon-alpha (IFNα) therapy alone is less effective in solid tumors. Autophagy has been reported to play a key role in tumor chemoresistance. Therefore, it is meaningful to explore whether autophagy can be activated by IFNα in head and neck squamous cell carcinoma (HNSCC) and serve as a potential target to improve efficacy of IFNα therapy. In this study, we report that IFNα not only exhibits anti-proliferation activity and induces apoptosis, but also activates autophagy in HNSCC cells. Moreover, silencing autophagy-related protein 5 (ATG5) and signal transducer and activator of transcription 1 (STAT1) suppresses autophagy flux. Furthermore, IFNα and autophagy inhibitors (hydroxychloroquine and wortmannin) show clear synergistic effects on inhibiting growth and promoting apoptosis in HNSCC cells and xenograft models. Our findings indicate that IFNα-induced autophagy plays a cytoprotective role and blocking autophagy flux promotes IFNα-mediated apoptosis in HNSCC. These results suggest that the combination of IFNα and autophagy inhibitors represents a novel strategy for HNSCC treatment.

Original languageEnglish (US)
Pages (from-to)34-47
Number of pages14
JournalCancer Letters
Volume451
DOIs
StatePublished - Jun 1 2019

Fingerprint

Autophagy
Interferon-alpha
Apoptosis
STAT1 Transcription Factor
Hydroxychloroquine
Carcinoma, squamous cell of head and neck
Heterografts
Neoplasms
Therapeutics
Growth

Keywords

  • Autophagy
  • Head and neck squamous cell carcinoma
  • Hydroxychloroquine
  • Interferon-alpha
  • Wortmannin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Blocking autophagy flux promotes interferon-alpha-mediated apoptosis in head and neck squamous cell carcinoma. / Yang, Wenyi; Jiang, Chunlan; Xia, Weiya; Ju, Houyu; Jin, Shufang; Liu, Shuli; Zhang, Liming; Ren, Guoxin; Ma, Hailong; Ruan, Min; Hu, Jingzhou.

In: Cancer Letters, Vol. 451, 01.06.2019, p. 34-47.

Research output: Contribution to journalArticle

Yang, Wenyi ; Jiang, Chunlan ; Xia, Weiya ; Ju, Houyu ; Jin, Shufang ; Liu, Shuli ; Zhang, Liming ; Ren, Guoxin ; Ma, Hailong ; Ruan, Min ; Hu, Jingzhou. / Blocking autophagy flux promotes interferon-alpha-mediated apoptosis in head and neck squamous cell carcinoma. In: Cancer Letters. 2019 ; Vol. 451. pp. 34-47.
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AU - Liu, Shuli

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