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 Resjournal_title
Cancer researchauthors
Lin SC,Chou YT,Jiang SS,Chang JL,Chung CH,Kao YR,Chang IS,Wu CWdoi
10.1158/0008-5472.CAN-15-3178subject
Has Abstractpub_date
2016-12-01 00:00:00pages
7036-7048issue
23eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-15-3178journal_volume
76pub_type
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