Cancer‐associated fibroblast‐derived Lumican promotes gastric cancer progression via the integrin β1‐FAK signaling pathway. Issue 5 (21st June 2017)

• Record Type: Journal Article
• Authors: Wang, Xiaofeng; Zhou, Quan; Yu, Zhenjia; Wu, Xiongyan; Chen, Xuehua; Li, Jianfang; Li, Chen; Yan, Min; Zhu, Zhenggang; Liu, Bingya; Su, Liping
• Is Part Of: International journal of cancer. Volume 141:Issue 5(2017:Sep. 01)
• Page Start: 998
• Page End: 1010
• Publication Date: 2017-06-21
• Subjects: gastric cancer -- cancer‐associated fibroblasts -- Lumican -- integrin β1‐FAK -- tumor progression; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.30801
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Gastric cancer (GC) is one of the most frequent malignant tumors worldwide and is associated with high invasiveness, high metastasis and poor prognosis. Cancer‐associated fibroblasts (CAFs), residing around tumor cells in tumor stroma, are important modifiers of tumor initiation and progression. However, the molecular mechanisms by which CAF's modulate tumor development have yet not to be characterized in GC. Here we performed tissue assay analyses identifying that Lumican, an extracellular matrix protein, is highly expressed in human gastric CAFs and its expression is positively associated with depth of invasion, lymph node metastasis, TNM stage and poor survival rate of GC. Functional studies revealed that integrin β1‐FAK signaling pathways mediate the promoting effect of Lumican on GC cell proliferation, migration and invasion in vitro . In accordance with these observations, in GC cells co‐cultured with CAFs in which Lumican had been knocked down, decreased gastric tumor growth and metastasis in vivo was apparent. In summary, CAF‐derived Lumican contributes to tumorigenesis and metastasis of GC by activating the integrin β1‐FAK signaling pathway. Abstract : What's new? Cancer‐associated fibroblasts (CAFs) can promote tumor progression and metastasis in gastric cancer (GC). However, the molecular mechanisms by which CAFs modulate tumor development are not well understood. In this study, the authors found that the extracellular‐matrix protein Lumican is highly expressed by CAFs in GC. This, in turn, activates the integrin β17FAK signaling pathway, which leads to increased tumor‐cell proliferation, migration and poor prognosis. Lumican may thus offer a potential therapeutic target in GC.