Oct4-related cytokine effects regulate tumorigenic properties of colorectal cancer cells.

Abstract:

:Oct4, a member of the POU-domain transcription factor family, has been implicated in the cancer stem cell (CSC)-like properties of various cancers. However, the precise role of Oct4 in colorectal CSC initiation remains uncertain. Numerous studies have demonstrated a strong link between inflammation and tumorigenesis in colorectal cancers. In this study, we demonstrated that Oct4 overexpression enhances CSC-like properties of colorectal cancer cells (CRCs), including sphere formation, cell colony formation, cell migration, invasiveness, and drug resistance. In addition, putative CSC markers, stemness genes, drug-resistant genes, as well as interleukin (IL)-8 and IL-32 were upregulated. Microarray-based bioinformatics of CRCs showed higher expression levels of embryonic stem cell-specific genes in cells that overexpressed Oct4. Neutralization of either IL-8 or IL-32 with specific antibodies partially blocked the tumorigenic effects induced by either Oct4 overexpression or by the addition of conditioned media from Oct4-overexpressing CRCs. In addition, the presence of Oct4-overexpressing CRCs enhanced the tumorigenic potential of parental CRCs in vivo. In summary, these data suggest that IL-8 and IL-32 play a role in regulating the CSC-like properties that promote tumorigenesis of CRCs in both autocrine and paracrine manners.

authors

Chang CJ,Chien Y,Lu KH,Chang SC,Chou YC,Huang CS,Chang CH,Chen KH,Chang YL,Tseng LM,Song WS,Wang JJ,Lin JK,Huang PI,Lan YT

doi

10.1016/j.bbrc.2011.10.024

subject

Has Abstract

pub_date

2011-11-18 00:00:00

pages

245-51

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(11)01821-3

journal_volume

415

pub_type

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