Adipocytes promote prostate cancer stem cell self-renewal through amplification of the cholecystokinin autocrine loop

Tang, Kai Dun, Liu, Ji, Jovanovic, Lidija, An, Jiyuan, Hill, Michelle M., Vela, Ian, Lee, Terence Kin-Wah, Ma, Stephanie, Nelson, Colleen, Russell, Pamela J., Clements, Judith A., & Ling, Ming-Tat (2016) Adipocytes promote prostate cancer stem cell self-renewal through amplification of the cholecystokinin autocrine loop. Oncotarget, 7(4), pp. 4939-4948.

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Abstract

Obesity has long been linked with prostate cancer progression, although the underlying mechanism is still largely unknown. Here, we report that adipocytes promote the enrichment of prostate cancer stem cells (CSCs) through a vicious cycle of autocrine amplification. In the presence of adipocytes, prostate cancer cells actively secrete the peptide hormone cholecystokinin (CCK), which not only stimulates prostate CSC self-renewal, but also induces cathepsin B (CTSB) production of the adipocytes. In return, CTSB facilitates further CCK secretion by the cancer cells. More importantly, inactivation of CCK receptor not only suppresses CTSB secretion by the adipocytes, but also synergizes the inhibitory effect of CTSB inhibitor on adipocyte-promoted prostate CSC self-renewal. In summary, we have uncovered a novel mechanism underlying the mutual interplay between adipocytes and prostate CSCs, which may help explaining the role of adipocytes in prostate cancer progression and provide opportunities for effective intervention.

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ID Code: 91044
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Adipocytes, Prostate cancer, Stem cell, Self-renewal, Amplification of the cholecustokinin autocrine loop
DOI: 10.18632/oncotarget.6643
ISSN: 1949-2553
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2016 Impact Journals, LLC
Deposited On: 07 Dec 2015 23:03
Last Modified: 28 Oct 2016 00:32

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