Periostin secreted by cancer-associated fibroblasts promotes cancer stemness in head and neck cancer by activating protein tyrosine kinase 7 (Retracted Article)
Periostin secreted by cancer-associated fibroblasts promotes cancer stemness in head and neck cancer by activating protein tyrosine kinase 7 (Retracted Article)
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癌症相关成纤维细胞分泌的骨膜素通过激活蛋白酪氨酸激酶7促进头颈癌的癌症干细胞性
DOI：
10.1038/s41419-018-1116-6
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发表时间：
2018-10-22
影响因子：
9
通讯作者：
Yan, Ming
中科院分区：
文献类型：
--
作者：
Yu, Binbin;Wu, Kailiu;Yan, Ming
蛋白酪氨酸激酶7 （PTK7）和癌症相关成纤维细胞（CAFs）分别在癌症严重度中起重要作用。然而，对于癌症中caf和PTK7之间的相互作用知之甚少。在本研究中，我们发现PTK7与人类头颈部鳞状细胞癌（HNSCC）的Wnt/ β - catenin通路和侵袭性临床病理特征显著相关。同时，动物实验显示PTK7在体内增强HNSCC的化疗耐药和肺转移。此外，共免疫沉淀（co-IP）实验表明，CAFs分泌的POSTN可能是PTK7的上游配体，可能作为受体。进一步分析发现，POSTN通过PTK7-Wnt/ β - catenin信号通路促进癌症干细胞（CSC）样表型，包括HNSCC细胞在体外的增殖和侵袭，以及体内肿瘤的发生和进展。总之，我们的研究证明，在HNSCC中，caff衍生的POSTN可能通过与PTK7的相互作用促进癌症的发生，这表明POSTN和PTK7的联合可能是一个潜在的预后和诊断指标，也是一个有希望的治疗靶点。
Protein tyrosine kinase 7 (PTK7) and cancer-associated fibroblasts (CAFs) play important roles in cancer sternness, 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/beta-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/beta-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.