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Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration.

Abstract：

:Following uncontrolled proliferation, a subset of primary tumour cells acquires additional traits/mutations to trigger phenotypic changes that enhance migration and are hypothesized to be the initiators of metastasis. This study reveals an adaptive mechanism that harnesses synergistic paracrine signalling via IL-6/8, which is amplified by cell proliferation and cell density, to directly promote cell migration. This effect occurs in metastatic human sarcoma and carcinoma cells- but not in normal or non-metastatic cancer cells-, and likely involves the downstream signalling of WASF3 and Arp2/3. The transcriptional phenotype of high-density cells that emerges due to proliferation resembles that of low-density cells treated with a combination of IL-6/8. Simultaneous inhibition of IL-6/8 receptors decreases the expression of WASF3 and Arp2/3 in a mouse xenograft model and reduces metastasis. This study reveals a potential mechanism that promotes tumour cell migration and infers a strategy to decrease metastatic capacity of tumour cells.

journal_name

Nat Commun

journal_title

Nature communications

authors

Jayatilaka H,Tyle P,Chen JJ,Kwak M,Ju J,Kim HJ,Lee JSH,Wu PH,Gilkes DM,Fan R,Wirtz D

doi

10.1038/ncomms15584

subject

Has Abstract

pub_date

2017-05-26 00:00:00

pages

15584

issn

2041-1723

pii

ncomms15584

journal_volume

8

pub_type

杂志文章

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