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

Despite therapeutic advancements, there’s been little alternation in the survival of patients with mind and neck squamous cell carcinoma (HNSCC). Recent results claim that cancer-connected fibroblasts (CAF) drive advancement of this ailment. Here, we are convinced that autophagy is upregulated in HNSCC-connected CAFs, where it accounts for key pathogenic contributions within this disease. Autophagy is essentially involved with cell degradation, but there’s emerging evidence that implies it’s also essential for cellular secretion. Thus, we hypothesized that autophagy-dependent secretion of tumor-promoting factors by HNSCC-connected CAFs may explain their role in malignant development. Meant for this hypothesis, we observed a decrease in CAF-facilitated HNSCC progression after blocking CAF autophagy. Studies of cell growth media conditioned after autophagy blockade revealed amounts of secreted IL6, IL8, along with other cytokines were modulated by autophagy. Particularly, when HNSCC cells were cocultured with SAR405 normal fibroblasts, they upregulated autophagy through IL6, IL8, and fundamental fibroblast growth factor. Inside a mouse xenograft type of HNSCC, pharmacologic inhibition of Vps34, a vital mediator of autophagy, enhanced the antitumor effectiveness 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.