Open AccessLoss of zinc‐finger protein 143 contributes to tumour progression by interleukin‐8‐CXCR axis in colon cancer
Author(s) -
Verma Vikas,
Paek A Rome,
Choi Beom-Kyu,
Hong Eun Kyung,
You Hye Jin
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14290
Subject(s) - biology , gene knockdown , intracellular , microbiology and biotechnology , cancer cell , secretion , stat protein , cancer research , kinase , signal transduction , tumor microenvironment , janus kinase , colorectal cancer , cancer , stat3 , cell culture , endocrinology , genetics
Several studies have shown that expression of zinc‐finger protein 143 (ZNF143) is closely related to tumour progression including colon cancer. However, it remains unclear how ZNF143 expression is related to tumour progression within the tumour microenvironment. Here, we investigated whether ZNF143 expression affects the tumour microenvironment and tumour progression by screening molecules secreted by colon cancer cells stably expressing short‐hairpin RNAs against ZNF143 or control RNAs. We observed that secretion of interleukin (IL)‐8 was increased when ZNF143 expression was reduced in two colon cancer cell lines. The mRNA and protein levels of IL‐8 were increased in cells following ZNF143 knockdown, and this effect was reversed when ZNF143 expression was restored. The Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) and extracellular signal‐regulated kinase pathways were also shown to contribute to IL‐8 expression in ZNF143‐knockdown cells. The expression levels of ZNF143 and IL‐8 were inversely correlated with three‐dimensionally grown spheroids and colon cancer tissues. THP‐1 cells were differentiated when cells were incubated with condition media from colon cancer cell with less ZNF143, drastically. Loss of ZNF143 may contribute to the development of colon cancer by regulating intracellular and intercellular signalling for cell plasticity and the tumour microenvironment respectively.