Open AccessWASH overexpression enhances cancer stem cell properties and correlates with poor prognosis of esophageal carcinoma
Author(s) -
Huang Lan,
Lian Jingyao,
Chen Xinfeng,
Qin Guohui,
Zheng Yujia,
Zhang Yi
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13400
Subject(s) - gene knockdown , cancer research , cancer , esophageal cancer , biology , cancer stem cell , actin cytoskeleton , metastasis , stem cell , cytoskeleton , cell culture , cell , microbiology and biotechnology , genetics
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.