PMID- 28914471 OWN - NLM STAT- MEDLINE DCOM- 20171212 LR - 20210109 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 108 IP - 12 DP - 2017 Dec TI - WASH overexpression enhances cancer stem cell properties and correlates with poor prognosis of esophageal carcinoma. PG - 2358-2365 LID - 10.1111/cas.13400 [doi] AB - 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. CI - (c) 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. FAU - Huang, Lan AU - Huang L AUID- ORCID: 0000-0001-6556-4067 AD - Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Lian, Jingyao AU - Lian J AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. FAU - Chen, Xinfeng AU - Chen X AD - Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Qin, Guohui AU - Qin G AD - Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Zheng, Yujia AU - Zheng Y AD - Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Zhang, Yi AU - Zhang Y AD - Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. LA - eng PT - Journal Article DEP - 20170926 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (Microfilament Proteins) RN - 0 (WASH protein, human) SB - IM MH - Animals MH - Carcinoma, Squamous Cell/*metabolism/mortality/*pathology MH - Esophageal Neoplasms/*metabolism/mortality/*pathology MH - Esophageal Squamous Cell Carcinoma MH - Heterografts MH - Humans MH - Kaplan-Meier Estimate MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Microfilament Proteins/*metabolism MH - Neoplastic Stem Cells/*metabolism/*pathology MH - Prognosis PMC - PMC5715296 OTO - NOTNLM OT - Cancer stem-like cell OT - Wiskott-Aldrich syndrome protein and SCAR Homolog (WASH) OT - esophageal squamous cell carcinoma OT - interleukin-8 OT - prognosis EDAT- 2017/09/16 06:00 MHDA- 2017/12/13 06:00 PMCR- 2017/12/01 CRDT- 2017/09/16 06:00 PHST- 2017/07/19 00:00 [received] PHST- 2017/09/07 00:00 [revised] PHST- 2017/09/12 00:00 [accepted] PHST- 2017/09/16 06:00 [pubmed] PHST- 2017/12/13 06:00 [medline] PHST- 2017/09/16 06:00 [entrez] PHST- 2017/12/01 00:00 [pmc-release] AID - CAS13400 [pii] AID - 10.1111/cas.13400 [doi] PST - ppublish SO - Cancer Sci. 2017 Dec;108(12):2358-2365. doi: 10.1111/cas.13400. Epub 2017 Sep 26.