Periostin（POSTN）是一种基质细胞蛋白，最初在成骨细胞中被鉴定出来。过去的研究已经表明，POSTN也更倾向于在不同类型的癌症中的癌相关成纤维细胞（CAFs）中表达。我们此前证明，在食管鳞状细胞癌（ESCC）患者的结缔组织中POSTN的表达增加与不利的临床结果相关。本研究旨在阐明POSTN在ESCC进展中的作用及其潜在的分子机制。我们发现，POSTN主要由ESCC组织中的CAFs产生，并且CAF培养基显著促进ESCC细胞系的迁移、侵袭、增殖和集落形成，这些作用依赖于POSTN。在ESCC细胞中，POSTN增加了ERK1 / 2的磷酸化并刺激了趋肽酶17（ADAM17）的表达和活性，后者在肿瘤发生和进展中起关键作用。通过使用中和POSTN的结合抗体干扰POSTN与整合素αvβ3或αvβ5的结合，可以抑制POSTN对ESCC细胞的影响。综上所述，我们的数据表明，CAFs来源的POSTN通过激活整合素αvβ3或αvβ5-ERK1 / 2途径刺激ADAM17活性，从而促进了ESCC的进展。版权所有©2023 Elsevier B.V.。保留所有权利。

Periostin (POSTN) is a matricellular protein that was originally identified in osteoblasts. Past studies have shown that POSTN is also preferentially expressed in cancer-associated fibroblasts (CAFs) in various types of cancer. We previously demonstrated that the increased expression of POSTN in stromal tissues is associated with an unfavorable clinical outcome in esophageal squamous cell carcinoma (ESCC) patients. In this study, we aimed to elucidate the role of POSNT in ESCC progression and its underlying molecular mechanism. We found that POSTN is predominantly produced by CAFs in ESCC tissues, and that CAFs-cultured media significantly promoted the migration, invasion, proliferation, and colony formation of ESCC cell lines in a POSTN-dependent manner. In ESCC cells, POSTN increased the phosphorylation of ERK1/2 and stimulated the expression and activity of a disintegrin and metalloproteinase 17 (ADAM17), which is critically involved in tumorigenesis and tumor progression. The effects of POSTN on ESCC cells were suppressed by interfering with the binding of POSTN to integrin αvβ3 or αvβ5 using neutralizing antibody against POSTN. Taken together, our data show that CAFs-derived POSTN stimulates ADAM17 activity through activation of the integrin αvβ3 or αvβ5-ERK1/2 pathway and thereby contributes to the progression of ESCC.Copyright © 2023 Elsevier B.V. All rights reserved.