V-ATPase-associated prorenin receptor is upregulated in prostate cancer after PTEN loss

Amro H. Mohammad, Sarah Assadian, Frédéric Couture, Karen J. Lefebvre, Wissal El-Assaad, Veronique Barrs, Veronique Ouellet, Pierre Luc Boulay, Jieyi Yang, Mathieu Latour, Luc Furic, William Muller, Nahum Sonenberg, Anne Marie Mes-Masson, Fred Saad, Robert Day, Jose G. Teodoro

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Phosphatase and tensin homolog (PTEN) tumor suppressor protein loss is common in prostate cancer (PCa). PTEN loss increases PI3K/Akt signaling, which promotes cell growth and survival. To find secreted biomarkers of PTEN loss, a proteomic screen was used to compare secretomes of cells with and without PTEN expression. We showed that PTEN downregulates Prorenin Receptor (PRR) expression and secretion of soluble Prorenin Receptor (sPRR) in PCa cells and in mouse. PRR is an accessory protein required for assembly of the vacuolar ATPase (V-ATPase) complex. V-ATPase is required for lysosomal acidification, amino acid sensing, efficient mechanistic target of Rapamycin complex 1 (mTORC1) activation, and β-Catenin signaling. On PCa tissue microarrays, PRR expression displayed a positive correlation with Akt phosphorylation. Moreover, PRR expression was required for proliferation of PCa cells by maintaining V-ATPase function. Further, we provided evidence for a potential clinical role for PRR expression and sPRR concentration in differentiating low from high Gleason grade PCa. Overall, the current study unveils a mechanism by which PTEN can inhibit tumor growth. Lower levels of PRR result in attenuated V-ATPase activity and reduced PCa cell proliferation.

Original languageEnglish
Pages (from-to)4923-4936
Number of pages14
JournalOncotarget
Volume10
Issue number48
DOIs
Publication statusPublished - 13 Aug 2019

Keywords

  • Prorenin receptor
  • Prostate cancer
  • PTEN
  • Soluble prorenin receptor
  • V-ATPase complex

Cite this

Mohammad, A. H., Assadian, S., Couture, F., Lefebvre, K. J., El-Assaad, W., Barrs, V., ... Teodoro, J. G. (2019). V-ATPase-associated prorenin receptor is upregulated in prostate cancer after PTEN loss. Oncotarget, 10(48), 4923-4936. https://doi.org/10.18632/oncotarget.27075
Mohammad, Amro H. ; Assadian, Sarah ; Couture, Frédéric ; Lefebvre, Karen J. ; El-Assaad, Wissal ; Barrs, Veronique ; Ouellet, Veronique ; Boulay, Pierre Luc ; Yang, Jieyi ; Latour, Mathieu ; Furic, Luc ; Muller, William ; Sonenberg, Nahum ; Mes-Masson, Anne Marie ; Saad, Fred ; Day, Robert ; Teodoro, Jose G. / V-ATPase-associated prorenin receptor is upregulated in prostate cancer after PTEN loss. In: Oncotarget. 2019 ; Vol. 10, No. 48. pp. 4923-4936.
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title = "V-ATPase-associated prorenin receptor is upregulated in prostate cancer after PTEN loss",
abstract = "Phosphatase and tensin homolog (PTEN) tumor suppressor protein loss is common in prostate cancer (PCa). PTEN loss increases PI3K/Akt signaling, which promotes cell growth and survival. To find secreted biomarkers of PTEN loss, a proteomic screen was used to compare secretomes of cells with and without PTEN expression. We showed that PTEN downregulates Prorenin Receptor (PRR) expression and secretion of soluble Prorenin Receptor (sPRR) in PCa cells and in mouse. PRR is an accessory protein required for assembly of the vacuolar ATPase (V-ATPase) complex. V-ATPase is required for lysosomal acidification, amino acid sensing, efficient mechanistic target of Rapamycin complex 1 (mTORC1) activation, and β-Catenin signaling. On PCa tissue microarrays, PRR expression displayed a positive correlation with Akt phosphorylation. Moreover, PRR expression was required for proliferation of PCa cells by maintaining V-ATPase function. Further, we provided evidence for a potential clinical role for PRR expression and sPRR concentration in differentiating low from high Gleason grade PCa. Overall, the current study unveils a mechanism by which PTEN can inhibit tumor growth. Lower levels of PRR result in attenuated V-ATPase activity and reduced PCa cell proliferation.",
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Mohammad, AH, Assadian, S, Couture, F, Lefebvre, KJ, El-Assaad, W, Barrs, V, Ouellet, V, Boulay, PL, Yang, J, Latour, M, Furic, L, Muller, W, Sonenberg, N, Mes-Masson, AM, Saad, F, Day, R & Teodoro, JG 2019, 'V-ATPase-associated prorenin receptor is upregulated in prostate cancer after PTEN loss', Oncotarget, vol. 10, no. 48, pp. 4923-4936. https://doi.org/10.18632/oncotarget.27075

V-ATPase-associated prorenin receptor is upregulated in prostate cancer after PTEN loss. / Mohammad, Amro H.; Assadian, Sarah; Couture, Frédéric; Lefebvre, Karen J.; El-Assaad, Wissal; Barrs, Veronique; Ouellet, Veronique; Boulay, Pierre Luc; Yang, Jieyi; Latour, Mathieu; Furic, Luc; Muller, William; Sonenberg, Nahum; Mes-Masson, Anne Marie; Saad, Fred; Day, Robert; Teodoro, Jose G.

In: Oncotarget, Vol. 10, No. 48, 13.08.2019, p. 4923-4936.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - V-ATPase-associated prorenin receptor is upregulated in prostate cancer after PTEN loss

AU - Mohammad, Amro H.

AU - Assadian, Sarah

AU - Couture, Frédéric

AU - Lefebvre, Karen J.

AU - El-Assaad, Wissal

AU - Barrs, Veronique

AU - Ouellet, Veronique

AU - Boulay, Pierre Luc

AU - Yang, Jieyi

AU - Latour, Mathieu

AU - Furic, Luc

AU - Muller, William

AU - Sonenberg, Nahum

AU - Mes-Masson, Anne Marie

AU - Saad, Fred

AU - Day, Robert

AU - Teodoro, Jose G.

PY - 2019/8/13

Y1 - 2019/8/13

N2 - Phosphatase and tensin homolog (PTEN) tumor suppressor protein loss is common in prostate cancer (PCa). PTEN loss increases PI3K/Akt signaling, which promotes cell growth and survival. To find secreted biomarkers of PTEN loss, a proteomic screen was used to compare secretomes of cells with and without PTEN expression. We showed that PTEN downregulates Prorenin Receptor (PRR) expression and secretion of soluble Prorenin Receptor (sPRR) in PCa cells and in mouse. PRR is an accessory protein required for assembly of the vacuolar ATPase (V-ATPase) complex. V-ATPase is required for lysosomal acidification, amino acid sensing, efficient mechanistic target of Rapamycin complex 1 (mTORC1) activation, and β-Catenin signaling. On PCa tissue microarrays, PRR expression displayed a positive correlation with Akt phosphorylation. Moreover, PRR expression was required for proliferation of PCa cells by maintaining V-ATPase function. Further, we provided evidence for a potential clinical role for PRR expression and sPRR concentration in differentiating low from high Gleason grade PCa. Overall, the current study unveils a mechanism by which PTEN can inhibit tumor growth. Lower levels of PRR result in attenuated V-ATPase activity and reduced PCa cell proliferation.

AB - Phosphatase and tensin homolog (PTEN) tumor suppressor protein loss is common in prostate cancer (PCa). PTEN loss increases PI3K/Akt signaling, which promotes cell growth and survival. To find secreted biomarkers of PTEN loss, a proteomic screen was used to compare secretomes of cells with and without PTEN expression. We showed that PTEN downregulates Prorenin Receptor (PRR) expression and secretion of soluble Prorenin Receptor (sPRR) in PCa cells and in mouse. PRR is an accessory protein required for assembly of the vacuolar ATPase (V-ATPase) complex. V-ATPase is required for lysosomal acidification, amino acid sensing, efficient mechanistic target of Rapamycin complex 1 (mTORC1) activation, and β-Catenin signaling. On PCa tissue microarrays, PRR expression displayed a positive correlation with Akt phosphorylation. Moreover, PRR expression was required for proliferation of PCa cells by maintaining V-ATPase function. Further, we provided evidence for a potential clinical role for PRR expression and sPRR concentration in differentiating low from high Gleason grade PCa. Overall, the current study unveils a mechanism by which PTEN can inhibit tumor growth. Lower levels of PRR result in attenuated V-ATPase activity and reduced PCa cell proliferation.

KW - Prorenin receptor

KW - Prostate cancer

KW - PTEN

KW - Soluble prorenin receptor

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Mohammad AH, Assadian S, Couture F, Lefebvre KJ, El-Assaad W, Barrs V et al. V-ATPase-associated prorenin receptor is upregulated in prostate cancer after PTEN loss. Oncotarget. 2019 Aug 13;10(48):4923-4936. https://doi.org/10.18632/oncotarget.27075