Epigenetic Switch between SOX2 and SOX9 Regulates Cancer Cell Plasticity.

Abstract:

:Cell differentiation within stem cell lineages can check proliferative potential, but nodal pathways that can limit tumor growth are obscure. Here, we report that lung cancer cell populations generate phenotypic and oncogenic plasticity via a switch between differentiation programs controlled by SOX2 and SOX9, thus altering proliferative and invasive capabilities. In lung cancer cells, SOX2 bound the EPCAM promoter to induce EpCAM-p21Cip1-cyclin A2 signaling, encouraging cell proliferation as well as barrier properties. In contrast, SOX9 bound the SLUG promoter to induce SLUG-mediated cell invasion with a spindle-like phenotype. Pharmacologic inhibition of HDAC elevated a SOX9-positive cell population from SOX2-positive cells, whereas ectopic expression of SOX2 inhibited SOX9 with increased H3K9me2 levels on the SOX9 promoter. In clinical specimens, the expression of SOX2 and SOX9 correlated negatively and positively with lung tumor grade, respectively. Our findings identify SOX2 and SOX9 as nodal epigenetic regulators in determining cancer cell plasticity and metastatic progression. Cancer Res; 76(23); 7036-48. ©2016 AACR.

journal_name

Cancer Res

journal_title

Cancer research

authors

Lin SC,Chou YT,Jiang SS,Chang JL,Chung CH,Kao YR,Chang IS,Wu CW

doi

10.1158/0008-5472.CAN-15-3178

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

7036-7048

issue

23

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-15-3178

journal_volume

76

pub_type

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