Secreted Hsp90 Is a Novel Regulator of the Epithelial to Mesenchymal Transition (EMT) in Prostate Cancer

Hance, Michael W.; Dole, K. K.; Gopal, Udhayakumar; Bohonowych, Jessica; Jezierska‐Drutel, Agnieszka; Neumann, Carola A.; Li, Haibo; Garraway, Isla P.; Isaacs, Jennifer S.

doi:10.1074/jbc.m112.389015

Cited by 126 publications

(174 citation statements)

References 88 publications

(106 reference statements)

Supporting

Mentioning

151

Contrasting

Order By: Relevance

“…At the same time, emerging evidence supporting the pleiotropic functions of extracellular Hsp90 (including innate immune signaling [38] as well as activation of matrix metalloproteinases potentially implicated in tissue remodeling [39,40]) suggests several plausible mechanisms through which citrullination of Hsp90 released from dying/apoptotic cells could influence the development of ILD. Even if citrullination of Hsp90␣/␤ subunits and the associated autoimmune responses are not directly responsible for initiating the disease processes in RA-ILD, the remarkably specific link between antibodies targeting citrullinated Hsp90 subunits and the development of RA-ILD is entirely consistent with a mechanistic paradigm in which injurious stimuli (e.g., smoking) elicit "danger responses" such as protein citrullination that, in turn, influence downstream signaling pathways as well as the host immune response.…”

Section: Discussionmentioning

confidence: 99%

Identification of Citrullinated Hsp90 Isoforms as Novel Autoantigens in Rheumatoid Arthritis–Associated Interstitial Lung Disease

Harlow¹,

Rosas²,

Gochuico³

et al. 2013

Arthritis & Rheumatism

122

View full text Add to dashboard Cite

Objective Subsets of patients with rheumatoid arthritis (RA) develop extraarticular complications that include interstitial lung disease (ILD). Because standardized algorithms for identification of RA patients at risk of developing clinically significant ILD are lacking, the purpose of this study was to elucidate unique serologic markers of RA‐associated ILD (RA‐ILD). Methods Sera from RA patients with ILD and from RA patients without ILD were used to immunoprecipitate citrullinated and uncitrullinated proteins derived from K562 cell extracts. Mass spectrometry was performed to facilitate identification of citrullinated proteins differentially immunoprecipitated by RA‐ILD patient sera. These candidate proteins were then used as substrate antigens in custom enzyme‐linked immunosorbent assays (ELISAs) for high‐throughput screening of sera obtained from cohorts of patients with RA, RA‐ILD mixed connective tissue disease (MCTD), or idiopathic pulmonary fibrosis (IPF). Results Differential immunoprecipitation and subsequent mass spectrometric sequencing identified citrullinated Hsp90α and citrullinated Hsp90β as candidate autoantigens in patients with RA‐ILD. ELISAs incorporating uncitrullinated and citrullinated isoforms of Hsp90 as substrate antigens demonstrated that sera from patients with RA‐ILD preferentially recognized citrullinated versions of Hsp90 with moderate sensitivity (range 20–30%) and great specificity (>95%) relative to sera derived from patients with RA alone (without ILD), patients with MCTD, or patients with IPF. Conclusion These studies demonstrate the utility of a novel autoantigen discovery method based on differential immunoprecipitation of citrullinated protein extracts. Application of these techniques identified citrullinated versions of Hsp90α and Hsp90β as autoantibody targets distinguishing RA‐ILD from RA without ILD, MCTD, and IPF, suggesting that anti–citrullinated Hsp90α/β autoantibodies may serve as effective biomarkers for the potentially devastating pulmonary manifestations of RA‐ILD.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Citrullinated Hsp90 Isoforms as Novel Autoantigens in Rheumatoid Arthritis–Associated Interstitial Lung Disease

Harlow¹,

Rosas²,

Gochuico³

et al. 2013

Arthritis & Rheumatism

122

View full text Add to dashboard Cite

show abstract

“…17). We demonstrated a unique role for eHsp90 as an initiator of EMT events in cell-based models of prostate cancer (18), thereby providing mechanistic relevancy for its tumorigenic function. Subsequent corroboration of eHsp90 as an EMT inducer in colon cancer (19) lends support for a conserved role for eHsp90 in malignancy.…”

mentioning

confidence: 99%

“…We reported previously the presence of surface Hsp90 in human prostatectomy specimens, further supporting a clinical role for eHsp90. Given that tumor surface Hsp90 correlates with elevated expression of transcripts encoding several key drivers of EMT (18), eHsp90 is emerging as a clinically relevant mediator of tumorigenic progression. Despite its growing importance, the accessory players cooperating with eHsp90 in malignancy, and particularly in prostate cancer, remain largely undefined.…”

mentioning

confidence: 99%

Tumor-secreted Hsp90 Subverts Polycomb Function to Drive Prostate Tumor Growth and Invasion

Nolan

Franco

Hance

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Extracellular Hsp90 (eHsp90) is implicated in cancer cell motility and invasion. Results: Tumor eHsp90 regulates ERK signaling, EZH2 expression, and histone methylation to facilitate prostate tumor growth and invasion. Conclusion: Newly characterized epigenetic functions of eHsp90 contribute to prostate tumorigenesis. Significance: Epigenetic modulation by eHsp90 may be a key facilitator in the transition of indolent to aggressive disease, highlighting a novel molecular effector of disease progression.

show abstract

“…The transcription factors that regulate the EMT are expressed in numerous malignant cancers. Increasing evidence and research suggests that the EMT has important functions in the malignant transformation of prostate cancer, and it also induces cancer cells to invade and migrate (Hance et al 2012;Lu et al 2012). Therefore, the EMT may be a potential therapeutic target, and inhibition of the EMT may be a promising method to treat cancer.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol suppresses the epithelial-to-mesenchymal transition in PC-3 cells by down-regulating the PI3K/AKT signaling pathway

Zhi

Tong

et al. 2016

Animal Cells and Systems

View full text Add to dashboard Cite

Resveratrol possesses a wide spectrum of pharmacological properties and has been an ideal alternative drug for the treatment of different cancers, including prostate cancer. However, the mechanisms by which resveratrol inhibits the growth of prostate cancer are still not fully elucidated. To understand the effect of resveratrol on the apoptosis and the epithelial-tomesenchymal transition (EMT) of prostate cancer as well as its related mechanism, we investigated the potential use of resveratrol in PC-3 prostate cancer cells in vitro using real-time PCR, fluorescence-activated cell sorting, Western blotting, etc. Resveratrol suppresses the PC-3 prostate cancer cell growth and induces apoptosis. Resveratrol also influences the expression of EMT-related proteins (increased E-cadherin and decreased Vimentin expression). Finally, resveratrol also suppressed Akt phosphorylation in PC-3 cells. This study indicates that resveratrol may be a potential anti-cancer treatment for prostate cancer; moreover, it provides new evidence that resveratrol suppresses prostate cancer growth and metastasis.ARTICLE HISTORY

show abstract

Secreted Hsp90 Is a Novel Regulator of the Epithelial to Mesenchymal Transition (EMT) in Prostate Cancer

Cited by 126 publications

References 88 publications

Identification of Citrullinated Hsp90 Isoforms as Novel Autoantigens in Rheumatoid Arthritis–Associated Interstitial Lung Disease

Identification of Citrullinated Hsp90 Isoforms as Novel Autoantigens in Rheumatoid Arthritis–Associated Interstitial Lung Disease

Tumor-secreted Hsp90 Subverts Polycomb Function to Drive Prostate Tumor Growth and Invasion

Resveratrol suppresses the epithelial-to-mesenchymal transition in PC-3 cells by down-regulating the PI3K/AKT signaling pathway

Contact Info

Product

Resources

About