WASH overexpression enhances cancer stem cell properties and correlates with poor prognosis of esophageal carcinoma. Issue 12 (26th September 2017)

• Record Type: Journal Article
• Authors: Huang, Lan; Lian, Jingyao; Chen, Xinfeng; Qin, Guohui; Zheng, Yujia; Zhang, Yi
• Is Part Of: Cancer science. Volume 108:Issue 12(2017)
• Page Start: 2358
• Page End: 2365
• Publication Date: 2017-09-26
• Subjects: Cancer stem‐like cell -- esophageal squamous cell carcinoma -- interleukin‐8 -- prognosis -- Wiskott‐Aldrich syndrome protein and SCAR Homolog (WASH); Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13400
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : There is increasing evidence that cytoskeleton remodeling is involved in cancer progression. Wiskott‐Aldrich syndrome protein (WASP) family represents a key regulator of actin cytoskeleton remodeling. However, the underlying mechanism of the WASP family in cancer progression remains elusive. Here, we studied the role of WASP and SCAR Homolog (WASH), a recently identified WASP family member, in human esophageal squamous cell carcinoma (ESCC). Using three human ESCC cell lines, we found that WASH expression was significantly elevated in cancer stem‐like cells enriched by sphere formation assay. WASH knockdown decreased the sphere‐forming capacity of esophageal cancer cells whereas WASH over‐expression exhibited the opposite effect. Mechanistically, we identified interleukin‐8 (IL‐8) as a key downstream target of WASH. IL‐8 knockdown completely attenuated tumor sphere formation induced by WASH overexpression. WASH knockdown also delayed the growth of human ESCC xenografts in BALB/c nude mice. Importantly, high WASH levels were associated with poor clinical prognosis in a total of 145 human ESCC tissues. Collectively, our results suggest an essential role of the WASH/IL‐8 pathway in human ESCC by maintaining the stemness of cancer cells. Hence, targeting this pathway might represent a promising strategy to control human esophageal carcinoma. Abstract : Our results suggest that overexpression of WASH drives secretion of IL‐8 to maintain cancer stem cell properties, likely contributing to progression of human esophageal cancer. Hence, targeting the WASH/IL‐8 pathway may represent a novel strategy to control human esophageal carcinoma.