Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer

Research output: Contribution to journal › Journal article › Research › peer-review

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Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer. / Al Nakouzi, Nader; Wang, Chris Kedong; Oo, Htoo Zarni; Nelepcu, Irina; Lallous, Nada; Spliid, Charlotte Bredo; Khazamipour, Nastaran; Lo, Joey; Truong, Sarah; Collins, Colin; Hui, Desmond; Esfandnia, Shaghayegh; Adomat, Hans; Clausen, Thomas Mandel; Gustavsson, Tobias; Choudhary, Swati; Dagil, Robert; Corey, Eva; Wang, Yuzhou; Chauchereau, Anne; Fazli, Ladan; Esko, Jeffrey D.; Salanti, Ali; Nelson, Peter S; Gleave, Martin; Daugaard, Mads.

In: Nature Communications, Vol. 13, 4760, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Al Nakouzi, N, Wang, CK, Oo, HZ, Nelepcu, I, Lallous, N, Spliid, CB, Khazamipour, N, Lo, J, Truong, S, Collins, C, Hui, D, Esfandnia, S, Adomat, H, Clausen, TM, Gustavsson, T, Choudhary, S, Dagil, R, Corey, E, Wang, Y, Chauchereau, A, Fazli, L, Esko, JD, Salanti, A, Nelson, PS, Gleave, M & Daugaard, M 2022, 'Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer', Nature Communications, vol. 13, 4760. https://doi.org/10.1038/s41467-022-32530-7

APA

Al Nakouzi, N., Wang, C. K., Oo, H. Z., Nelepcu, I., Lallous, N., Spliid, C. B., Khazamipour, N., Lo, J., Truong, S., Collins, C., Hui, D., Esfandnia, S., Adomat, H., Clausen, T. M., Gustavsson, T., Choudhary, S., Dagil, R., Corey, E., Wang, Y., ... Daugaard, M. (2022). Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer. Nature Communications, 13, [4760]. https://doi.org/10.1038/s41467-022-32530-7

Vancouver

Al Nakouzi N, Wang CK, Oo HZ, Nelepcu I, Lallous N, Spliid CB et al. Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer. Nature Communications. 2022;13. 4760. https://doi.org/10.1038/s41467-022-32530-7

Author

Al Nakouzi, Nader ; Wang, Chris Kedong ; Oo, Htoo Zarni ; Nelepcu, Irina ; Lallous, Nada ; Spliid, Charlotte Bredo ; Khazamipour, Nastaran ; Lo, Joey ; Truong, Sarah ; Collins, Colin ; Hui, Desmond ; Esfandnia, Shaghayegh ; Adomat, Hans ; Clausen, Thomas Mandel ; Gustavsson, Tobias ; Choudhary, Swati ; Dagil, Robert ; Corey, Eva ; Wang, Yuzhou ; Chauchereau, Anne ; Fazli, Ladan ; Esko, Jeffrey D. ; Salanti, Ali ; Nelson, Peter S ; Gleave, Martin ; Daugaard, Mads. / Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer. In: Nature Communications. 2022 ; Vol. 13.

Bibtex

@article{c9f2667fbe524d65bce9d9af325c01bc,
title = "Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer",
abstract = "Lineage plasticity of prostate cancer is associated with resistance to androgen receptor (AR) pathway inhibition (ARPI) and supported by a reactive tumor microenvironment. Here we show that changes in chondroitin sulfate (CS), a major glycosaminoglycan component of the tumor cell glycocalyx and extracellular matrix, is AR-regulated and promotes the adaptive progression of castration-resistant prostate cancer (CRPC) after ARPI. AR directly represses transcription of the 4-O-sulfotransferase gene CHST11 under basal androgen conditions, maintaining steady-state CS in prostate adenocarcinomas. When AR signaling is inhibited by ARPI or lost during progression to non-AR-driven CRPC as a consequence of lineage plasticity, CHST11 expression is unleashed, leading to elevated 4-O-sulfated chondroitin levels. Inhibition of the tumor cell CS glycocalyx delays CRPC progression, and impairs growth and motility of prostate cancer after ARPI. Thus, a reactive CS glycocalyx supports adaptive survival and treatment resistance after ARPI, representing a therapeutic opportunity in patients with advanced prostate cancer.",
author = "{Al Nakouzi}, Nader and Wang, {Chris Kedong} and Oo, {Htoo Zarni} and Irina Nelepcu and Nada Lallous and Spliid, {Charlotte Bredo} and Nastaran Khazamipour and Joey Lo and Sarah Truong and Colin Collins and Desmond Hui and Shaghayegh Esfandnia and Hans Adomat and Clausen, {Thomas Mandel} and Tobias Gustavsson and Swati Choudhary and Robert Dagil and Eva Corey and Yuzhou Wang and Anne Chauchereau and Ladan Fazli and Esko, {Jeffrey D.} and Ali Salanti and Nelson, {Peter S} and Martin Gleave and Mads Daugaard",
year = "2022",
doi = "10.1038/s41467-022-32530-7",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer

AU - Al Nakouzi, Nader

AU - Wang, Chris Kedong

AU - Oo, Htoo Zarni

AU - Nelepcu, Irina

AU - Lallous, Nada

AU - Spliid, Charlotte Bredo

AU - Khazamipour, Nastaran

AU - Lo, Joey

AU - Truong, Sarah

AU - Collins, Colin

AU - Hui, Desmond

AU - Esfandnia, Shaghayegh

AU - Adomat, Hans

AU - Clausen, Thomas Mandel

AU - Gustavsson, Tobias

AU - Choudhary, Swati

AU - Dagil, Robert

AU - Corey, Eva

AU - Wang, Yuzhou

AU - Chauchereau, Anne

AU - Fazli, Ladan

AU - Esko, Jeffrey D.

AU - Salanti, Ali

AU - Nelson, Peter S

AU - Gleave, Martin

AU - Daugaard, Mads

PY - 2022

Y1 - 2022

N2 - Lineage plasticity of prostate cancer is associated with resistance to androgen receptor (AR) pathway inhibition (ARPI) and supported by a reactive tumor microenvironment. Here we show that changes in chondroitin sulfate (CS), a major glycosaminoglycan component of the tumor cell glycocalyx and extracellular matrix, is AR-regulated and promotes the adaptive progression of castration-resistant prostate cancer (CRPC) after ARPI. AR directly represses transcription of the 4-O-sulfotransferase gene CHST11 under basal androgen conditions, maintaining steady-state CS in prostate adenocarcinomas. When AR signaling is inhibited by ARPI or lost during progression to non-AR-driven CRPC as a consequence of lineage plasticity, CHST11 expression is unleashed, leading to elevated 4-O-sulfated chondroitin levels. Inhibition of the tumor cell CS glycocalyx delays CRPC progression, and impairs growth and motility of prostate cancer after ARPI. Thus, a reactive CS glycocalyx supports adaptive survival and treatment resistance after ARPI, representing a therapeutic opportunity in patients with advanced prostate cancer.

AB - Lineage plasticity of prostate cancer is associated with resistance to androgen receptor (AR) pathway inhibition (ARPI) and supported by a reactive tumor microenvironment. Here we show that changes in chondroitin sulfate (CS), a major glycosaminoglycan component of the tumor cell glycocalyx and extracellular matrix, is AR-regulated and promotes the adaptive progression of castration-resistant prostate cancer (CRPC) after ARPI. AR directly represses transcription of the 4-O-sulfotransferase gene CHST11 under basal androgen conditions, maintaining steady-state CS in prostate adenocarcinomas. When AR signaling is inhibited by ARPI or lost during progression to non-AR-driven CRPC as a consequence of lineage plasticity, CHST11 expression is unleashed, leading to elevated 4-O-sulfated chondroitin levels. Inhibition of the tumor cell CS glycocalyx delays CRPC progression, and impairs growth and motility of prostate cancer after ARPI. Thus, a reactive CS glycocalyx supports adaptive survival and treatment resistance after ARPI, representing a therapeutic opportunity in patients with advanced prostate cancer.

U2 - 10.1038/s41467-022-32530-7

DO - 10.1038/s41467-022-32530-7

M3 - Journal article

C2 - 35963852

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 4760

ER -

ID: 316420856