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The SUMO Ligase PIAS1 Promotes the Progression and Survival of Solid Tumors of Different Histopathological Origins
Author(s) -
Constanzo Jerfiz D,
Rabellino Andrea,
Konstantinidou Georgia,
Schuster Katja,
Scaglioni Pier
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1027.8
Subject(s) - cancer research , small hairpin rna , carcinogenesis , ubiquitin ligase , cell growth , tumor progression , cell culture , biology , cancer , chemistry , ubiquitin , gene knockdown , genetics , gene
Protein inhibitor of activated STAT‐1 (PIAS1) regulates cell signaling via posttranslational modifications of proteins. PIAS1 conjugates small ubiquitin like modifiers (SUMO‐chains) onto target proteins. Our lab discovered that PIAS1 SUMOylates the promyelocytic leukemia (PML) tumor suppressor. This event promotes degradation of the tumor suppressor (PML) aiding tumor progression. Thus, we hypothesized that PIAS1 will promote cell survival and progression in human cancers where it is highly expressed, representing an unexplored vulnerability in these cancers. We performed gain and loss of function experiments to test PIAS1 effect on tumorigenesis with transformation assays, and studied cell survival after PIAS1 depletion using RNAi. Ectopic overexpression of Pias1 protein in NIH3T3 and mouse embryonic fibroblasts (MEFs) promotes colony formation and loss of contact inhibition in culture. PIAS1 depletion using shRNA in non‐small cell lung cancer (NSCLC) and breast cancer cell lines leads to increased PML levels, following susceptibility to apoptosis and impaired cell proliferation. Moreover, siRNA depletion of PIAS1 in NSCLC cell line H460 reduces cell spreading and impairs migration in wound healing assays. Our findings show for the first time a novel role for the SUMO ligase PIAS1 in tumor progression and survival. Our findings lay the groundwork for the study of PIAS1 in human cancers.