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Global transcriptional analysis of different HT1080 cell phenotypes induced by cell proliferation and density

ABSTRACT: Following uncontrolled proliferation, a subset of primary tumor cells acquires additional traits/mutations to trigger phenotypic changes that enhance migration and are hypothesized to be the initiations of metastasis. This study reveals a novel adaptive mechanism that harnesses synergistic paracrine signaling 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 non-metastatic cells-, through the downstream signaling of WASF3 and Arp2/3. Our RNA-seq based global transcriptional analysis showed that 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 significantly decreases the expression of WASF3 and Arp2/3 in a mouse xenograft model and consequently reduces metastasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE96817 | GEO | 2017/03/25

SECONDARY ACCESSION(S): PRJNA379815

REPOSITORIES: GEO

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