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

Nolan, Krystal D.; Franco, Omar E.; Hance, Michael W.; Hayward, Simon W.; Isaacs, Jennifer S.

doi:10.1074/jbc.m115.637496

Cited by 70 publications

(75 citation statements)

References 56 publications

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“…As many of the properties of cancer resemble those found in wound healing this suggested a potential role in malignancy. Indeed, a number of studies suggest a role for extracellular Hsp90 in stimulation of metastasis, involving a range of mechanisms[96, 97]. Hsp90 appears to have a profound influence on would healing, EMT and metastasis through this “inside out” signaling cascade (Figure 5).…”

Section: Extracellular Chaperones: the Jokers In The Packmentioning

confidence: 99%

Heat Shock Proteins Promote Cancer: It's a Protection Racket

Calderwood

Gong

2016

Trends in Biochemical Sciences

334

251

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Heat Shock Proteins (HSP) are expressed at high levels in cancer and form a fostering environment essential for tumor development. We have reviewed the recent data in this area, concentrating mainly on Hsp27, Hsp70 and Hsp90. The overriding role of the HSPs in cancer is to stabilize the active functions of overexpressed and mutated cancer gene. Elevated HSPs are thus required for many of the traits that underlie the morbidity of cancer, including increased growth, survival and formation of secondary cancers. In addition, HSPs participate in the evolution of cancer treatment resistance. HSPs are also released from cancer cells and influence malignant properties by receptor- mediated signaling. Current data strongly support efforts to target HSPs in cancer treatment.

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Section: Extracellular Chaperones: the Jokers In The Packmentioning

confidence: 99%

Heat Shock Proteins Promote Cancer: It's a Protection Racket

Calderwood

Gong

2016

Trends in Biochemical Sciences

334

251

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“…Signaling by TGF-β and BMP regulates EMT, invasion, and survival in NSCLC (Hsu et al, 2011; Nolan et al, 2015). TGF-β and BMP binding to a heterodimeric receptor complex with type I and type II components activates downstream signaling, with direct effectors that include SMAD1, 5, and 8 as well as multiple additional proteins that support survival signaling, such as NFκB, β-catenin and others (Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

Anti-Müllerian Hormone Signaling Regulates Epithelial Plasticity and Chemoresistance in Lung Cancer

et al. 2016

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Summary Anti-Müllerian hormone (AMH) and its type II receptor AMHR2, both previously thought to primarily function in gonadal tissue, were unexpectedly identified as potent regulators of TGF-β/BMP signaling and epithelial-mesenchymal transition (EMT) in lung cancer. AMH is a TGF-β/BMP superfamily member, and AMHR2 heterodimerizes with type I receptors (ALK2, ALK3) also used by the type II receptor for BMP (BMPR2). AMH signaling regulates expression of BMPR2, ALK2 and ALK3, supports AKT-NFκB and SMAD survival signaling, and influences BMP-dependent signaling in NSCLC. AMH and AMHR2 are selectively expressed in epithelial versus mesenchymal cells, and loss of AMH/AMHR2 induces EMT. Independent induction of EMT reduces expression of AMH and AMHR2. Importantly, EMT associated with depletion of AMH or AMHR2 results in chemoresistance, but sensitizes cells to the HSP90 inhibitor ganetespib. Recognition of this AMH/AMHR2 axis helps to further elucidate TGF-β/BMP resistance-associated signaling and suggests new strategies for therapeutic targeting of EMT.

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“…They were subcultured to approximately 80% confluency prior to harvest for nuclei isolation. [33–35] WA09 hESCs were grown in media containing HEREGULIN β1 (10 ng/ml; Peprotech), ACTIVIN A (10 ng/ml; R&D Systems), and human LONGR3 insulin-like growth factor 1 (IGF-1; 200 ng/ml; Sigma) and harvested at confluency. [36–37] The U937 (ATCC® CRL-1593.2™) and U1 (NIH AIDS Reagent Program #165) pleural effusion, lymphocyte cell line was grown in a humidified incubator at 37ºC and 5% CO2.…”

Section: Methodsmentioning

confidence: 99%

Label-Free Relative Quantitation of Isobaric and Isomeric Human Histone H2A and H2B Variants by Fourier Transform Ion Cyclotron Resonance Top-Down MS/MS

et al. 2016

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Histone variants are known to play a central role in genome regulation and maintenance. However, many variants are inaccessible by antibody-based methods or bottom-up tandem mass spectrometry due to their highly similar sequences. For many, the only tractable approach is with intact protein top-down tandem mass spectrometry. Here, ultrahigh-resolution FT-ICR MS and MS/MS yield quantitative relative abundances of all detected HeLa H2A and H2B isobaric and isomeric variants with a label-free approach. We extend the analysis to identify and relatively quantitate 16 proteoforms from 12 sequence variants of histone H2A and 10 proteoforms of histone H2B from three other cell lines: human embryonic stem cells (WA09), U937, and a prostate cancer cell line LaZ. The top-down MS/MS approach provides a path forward for more extensive elucidation of the biological role of many previously unstudied histone variants and post-translational modifications.

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

Cited by 70 publications

References 56 publications

Heat Shock Proteins Promote Cancer: It's a Protection Racket

Heat Shock Proteins Promote Cancer: It's a Protection Racket

Anti-Müllerian Hormone Signaling Regulates Epithelial Plasticity and Chemoresistance in Lung Cancer

Label-Free Relative Quantitation of Isobaric and Isomeric Human Histone H2A and H2B Variants by Fourier Transform Ion Cyclotron Resonance Top-Down MS/MS

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