Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
Cancer Sci. 2022 Aug;113(8):2704-2715. doi: 10.1111/cas.15452. Epub 2022 Jun 16.
Elevated adenosine generated by CD73 (ecto-5'-nucleotidase; NT5E) could boost immunosuppressive responses and promote immune evasion in the tumor microenvironment. However, despite the immune response, CD73 could also promote tumor progression in a variety of cancers, and the nonimmunologic role and corresponding molecular mechanism of CD73 involved in head and neck squamous cell carcinoma (HNSCC) progression are not well characterized. Here, we demonstrated that CD73/NT5E is overexpressed in HNSCC tissues and predicts poor prognosis. Suppression of CD73 inhibited the proliferation, migration, and invasion of HNSCC cell lines (CAL27 and HN4) in vitro and in vivo. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) predicted that CD73 may be involved in invadopodia formation and MAPK signaling activation. As expected, knockdown of CD73 inhibited the MAPK signaling pathway, and the suppressive effect of CD73 knockdown on proliferation, migration, invasion, and invadopodia formation was reversed by a MAPK signaling activator. Our results suggest that CD73 could promote the proliferation, migration, invasion, and invadopodia formation of HNSCC via the MAPK signaling pathway and provide new mechanistic insights into the nonimmunological role of CD73 in HNSCC.
CD73（外核苷酸酶 5'-核苷酸；NT5E）产生的升高的腺苷可能会增强肿瘤微环境中的免疫抑制反应并促进免疫逃逸。然而，尽管存在免疫反应，但 CD73 也可以在多种癌症中促进肿瘤进展，并且 CD73 在头颈部鳞状细胞癌（HNSCC）进展中涉及的非免疫作用和相应的分子机制尚未得到很好的描述。在这里，我们证明 CD73/NT5E 在 HNSCC 组织中过表达，并预测预后不良。体外和体内抑制 CD73 抑制了 HNSCC 细胞系（CAL27 和 HN4）的增殖、迁移和侵袭。基因集变异分析（GSVA）和基因集富集分析（GSEA）预测 CD73 可能参与了侵袭伪足的形成和 MAPK 信号通路的激活。正如预期的那样，CD73 的敲低抑制了 MAPK 信号通路，并且 MAPK 信号通路激活剂逆转了 CD73 敲低对增殖、迁移、侵袭和侵袭伪足形成的抑制作用。我们的结果表明，CD73 可以通过 MAPK 信号通路促进 HNSCC 的增殖、迁移、侵袭和侵袭伪足的形成，并为 CD73 在 HNSCC 中的非免疫作用提供新的机制见解。
