American Association for Cancer Research
Browse
00085472can171077-sup-181786_3_supp_4282689_wwlbhm.pdf (210.45 kB)

Figure S2 from Secretory Autophagy in Cancer-Associated Fibroblasts Promotes Head and Neck Cancer Progression and Offers a Novel Therapeutic Target

Download (210.45 kB)
journal contribution
posted on 2023-03-31, 01:02 authored by Jacob New, Levi Arnold, Megha Ananth, Sameer Alvi, Mackenzie Thornton, Lauryn Werner, Ossama Tawfik, Hongying Dai, Yelizaveta Shnayder, Kiran Kakarala, Terance T. Tsue, Douglas A. Girod, Wen-Xing Ding, Shrikant Anant, Sufi Mary Thomas

CAF autophagy inhibition significantly decreases HNSCC in vitro progression.

Funding

University of Kansas Cancer Center

NIH

University of Kansas Medical Center

KUMC

NIGMS

History

ARTICLE ABSTRACT

Despite therapeutic advancements, there has been little change in the survival of patients with head and neck squamous cell carcinoma (HNSCC). Recent results suggest that cancer-associated fibroblasts (CAF) drive progression of this disease. Here, we report that autophagy is upregulated in HNSCC-associated CAFs, where it is responsible for key pathogenic contributions in this disease. Autophagy is fundamentally involved in cell degradation, but there is emerging evidence that suggests it is also important for cellular secretion. Thus, we hypothesized that autophagy-dependent secretion of tumor-promoting factors by HNSCC-associated CAFs may explain their role in malignant development. In support of this hypothesis, we observed a reduction in CAF-facilitated HNSCC progression after blocking CAF autophagy. Studies of cell growth media conditioned after autophagy blockade revealed levels of secreted IL6, IL8, and other cytokines were modulated by autophagy. Notably, when HNSCC cells were cocultured with normal fibroblasts, they upregulated autophagy through IL6, IL8, and basic fibroblast growth factor. In a mouse xenograft model of HNSCC, pharmacologic inhibition of Vps34, a key mediator of autophagy, enhanced the antitumor efficacy of cisplatin. Our results establish an oncogenic function for secretory autophagy in HNSCC stromal cells that promotes malignant progression. Cancer Res; 77(23); 6679–91. ©2017 AACR.

Usage metrics

    Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC