p62/SQSTM1 is required for cell survival of apoptosis-resistant bone metastatic prostate cancer cell lines

dc.citation.firstpage149en_US
dc.citation.issueNumber2en_US
dc.citation.journalTitleThe Prostateen_US
dc.citation.lastpage163en_US
dc.citation.volumeNumber74en_US
dc.contributor.authorChang, Megan A.en_US
dc.contributor.authorMorgado, Micaelaen_US
dc.contributor.authorWarren, Curtis R.en_US
dc.contributor.authorHinton, Cimona V.en_US
dc.contributor.authorFarach-Carson, Mary C.en_US
dc.contributor.authorDelk, Nikki A.en_US
dc.date.accessioned2017-06-14T16:55:02Z
dc.date.available2017-06-14T16:55:02Z
dc.date.issued2014en_US
dc.description.abstractBACKGROUND: Bone marrow stromal cell (BMSC) paracrine factor(s) can induce apoptosis in bone metastatic prostate cancer (PCa) cell lines. However, the PCa cells that escape BMSC-induced apoptosis can upregulate cytoprotective autophagy. METHODS: C4-2, C4-2B, MDA PCa 2a, MDA PCa 2b, VCaP, PC3, or DU145 PCa cell lines were grown in BMSC conditioned medium and analyzed for mRNA and/or protein accumulation of p62 (also known as sequestome-1/SQSTM1), Microtubule-associated protein 1 light chain 3B (LC3B), or lysosomal-associated membrane protein 1 (LAMP1) using quantitative polymerase chain reaction (QPCR), Western blot, or immunofluorescence. Small interfering RNA (siRNA) was used to determine if p62 is necessary PCa cell survival. RESULTS: BMSC paracrine signaling upregulated p62 mRNA and protein in a subset of the PCa cell lines. The PCa cell lines that were insensitive to BMSC-induced apoptosis and autophagy induction had elevated basal p62 mRNA and protein. In the BMSC-insensitive PCa cell lines, siRNA knockdown of p62 was cytotoxic and immunostaining showed peri-nuclear clustering of autolysosomes. However, in the BMSC-sensitive PCa cell lines, p62 siRNA knockdown was not appreciably cytotoxic and did not affect autolysosome subcellular localization. CONCLUSIONS: A pattern emerges wherein the BMSC-sensitive PCa cell lines are known to be osteoblastic and express the androgen receptor, while the BMSC-insensitive PCa cell lines are characteristically osteolytic and do not express the androgen receptor. Furthermore, BMSC-insensitive PCa may have evolved a dependency on p62 for cell survival that could be exploited to target and kill these apoptosis-resistant PCa cells in the bone.en_US
dc.identifier.citationChang, Megan A., Morgado, Micaela, Warren, Curtis R., et al.. "p62/SQSTM1 is required for cell survival of apoptosis-resistant bone metastatic prostate cancer cell lines." <i>The Prostate,</i> 74, no. 2 (2014) Wiley: 149-163. https://doi.org/10.1002/pros.22737.
dc.identifier.doihttps://doi.org/10.1002/pros.22737en_US
dc.identifier.urihttps://hdl.handle.net/1911/94842
dc.language.isoengen_US
dc.publisherWiley
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Wiley.en_US
dc.subject.keywordautophagyen_US
dc.subject.keywordbone marrowen_US
dc.subject.keywordbone paracrine factorsen_US
dc.subject.keywordp62/SQSTM1en_US
dc.subject.keywordprostate canceren_US
dc.titlep62/SQSTM1 is required for cell survival of apoptosis-resistant bone metastatic prostate cancer cell linesen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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