American Association for Cancer Research
19406207capr160089-sup-164706_1_supp_3488426_66zggj.png (64.59 kB)

Supplemental Figure S1 from STAT3 as a Chemoprevention Target in Carcinogen-Induced Head and Neck Squamous Cell Carcinoma

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posted on 2023-04-03, 22:00 authored by Noah D. Peyser, Lin Wang, Yan Zeng, Marie Acquafondata, Maria Freilino, Hua Li, Malabika Sen, William E. Gooding, Masanobu Satake, Zhenghe Wang, Daniel E. Johnson, Jennifer R. Grandis

Parallel slopes indicate identical response to Stattic in PTPRT WT and KO mice. Vertical distance indicates improved outcome of Stattic-treated mice compared to vehicle-treated.






Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal disease due, in large part, to a high rate of second primary tumor (SPT) formation. The 4-nitroquinoline 1-oxide (4-NQO) mouse model of oral carcinogenesis provides a robust system in which to study chemopreventive agents in the context of chemically induced HNSCC tumors. STAT3 is a potent oncogene that is hyperactivated by tyrosine phosphorylation early in HNSCC carcinogenesis and is a rational therapeutic target. We recently reported that loss-of-function of the STAT3 phosphatase PTPRT promotes STAT3 activation in HNSCC tumors and preclinical models and may serve as a predictive biomarker of response to STAT3 inhibitors, including the small-molecule Stattic. We therefore investigated the hypothesis that Ptprt-knockout (KO) mice would be more susceptible to 4-NQO–induced oral carcinogenesis and more sensitive to Stattic-mediated chemoprevention compared with wild-type (WT) mice. Herein, we demonstrate that Ptprt WT and KO mice develop similar spectra of HNSCC disease severity upon 12 weeks of 4-NQO administration, with no apparent effect of Ptprt genotype on carcinogenesis or treatment outcome. Targeting of STAT3 with Stattic resulted in a chemopreventive effect against 4-NQO–induced oral cancer (P = 0.0402). While these results do not support a central role for PTPRT in 4-NQO–induced HNSCC carcinogenesis, further investigation of STAT3 as a chemoprevention target in this cancer is warranted. Cancer Prev Res; 9(8); 657–63. ©2016 AACR.