Department of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital & College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
National Clinical Research Center of Stomatology, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
Cell Death Dis. 2018 Oct 22;9(11):1082. doi: 10.1038/s41419-018-1116-6.
Protein tyrosine kinase 7 (PTK7) and cancer-associated fibroblasts (CAFs) play important roles in cancer stemness, respectively. However, little is known about interaction between CAFs and PTK7 in cancers. In this study, we showed that PTK7 was significantly correlated with the Wnt/β-Catenin pathway and aggressive clinicopathologic features in human head and neck squamous cell carcinoma (HNSCC). Meanwhile, animal experiments showed that PTK7 enhanced chemoresistance and lung metastasis of HNSCC in vivo. In addition, co-immunoprecipitation (co-IP) assay demonstrated that POSTN secreted by CAFs was a potential upstream ligand of PTK7 which might act as a receptor. Further analysis revealed that POSTN promoted the cancer stem cell (CSC)-like phenotype via PTK7-Wnt/β-Catenin signaling, including the proliferation and invasion of HNSCC cells in vitro, as well as tumor initiation and progression in vivo. Collectively, our study proved that CAF-derived POSTN might promote cancer stemness via interacting with PTK7 in HNSCC, suggesting that the combination of POSTN and PTK7 might be a potential prognostic and diagnostic indicator and a promising therapeutic target.
蛋白酪氨酸激酶 7（PTK7）和癌相关成纤维细胞（CAFs）分别在癌症干性中发挥重要作用。然而，CAFs 和 PTK7 之间在癌症中的相互作用知之甚少。在这项研究中，我们表明 PTK7 与人头颈部鳞状细胞癌（HNSCC）中的 Wnt/β-连环蛋白通路和侵袭性临床病理特征显著相关。同时，动物实验表明，PTK7 增强了 HNSCC 的化疗耐药性和肺转移。此外，免疫共沉淀（co-IP）实验表明，CAFs 分泌的 POSTN 是 PTK7 的潜在上游配体，可能作为受体发挥作用。进一步分析表明，POSTN 通过 PTK7-Wnt/β-连环蛋白信号促进癌症干细胞（CSC）样表型，包括体外 HNSCC 细胞的增殖和侵袭，以及体内肿瘤起始和进展。总之，我们的研究证明了 CAF 衍生的 POSTN 可能通过与 HNSCC 中的 PTK7 相互作用来促进癌症干性，这表明 POSTN 和 PTK7 的组合可能是一个有前途的治疗靶点和潜在的预后和诊断标志物。
