Antagonism of tumoral prolactin receptor promotes autophagy-related cell death

Yunfei Wen; Behrouz Zand; Bulent Ozpolat; Miroslaw J Szczepanski; Chunhua Lu; Erkan Yuca; Amy R Carroll; Neslihan Alpay; Chandra Bartholomeusz; Ibrahim Tekedereli; Yu Kang; Rajesha Rupaimoole; Chad V Pecot; Heather J Dalton; Anadulce Hernandez; Anna Lokshin; Susan K Lutgendorf; Jinsong Liu; Walter N Hittelman; Wen Y Chen; Gabriel Lopez-Berestein; Marta Szajnik; Naoto T Ueno; Robert L Coleman; Anil K Sood

doi:10.1016/j.celrep.2014.03.009

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Antagonism of tumoral prolactin receptor promotes autophagy-related cell death

Journal article

Open access

Peer reviewed

Antagonism of tumoral prolactin receptor promotes autophagy-related cell death

Yunfei Wen, Behrouz Zand, Bulent Ozpolat, Miroslaw J Szczepanski, Chunhua Lu, Erkan Yuca, Amy R Carroll, Neslihan Alpay, Chandra Bartholomeusz, Ibrahim Tekedereli, …

Cell reports (Cambridge), Vol.7(2), pp.488-500

04/24/2014

DOI: 10.1016/j.celrep.2014.03.009

PMCID: PMC4038960

PMID: 24703838

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https://doi.org/10.1016/j.celrep.2014.03.009View

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Abstract

Therapeutic upregulation of macroautophagy in cancer cells provides an alternative mechanism for cell death. Prolactin (PRL) and its receptor (PRLR) are considered attractive therapeutic targets because of their roles as growth factors in tumor growth and progression. We utilized G129R, an antagonist peptide of PRL, to block activity of the tumoral PRL/PRLR axis, which resulted in inhibition of tumor growth in orthotopic models of human ovarian cancer. Prolonged treatment with G129R induced the accumulation of redundant autolysosomes in 3D cancer spheroids, leading to a type II programmed cell death. This inducible autophagy was a noncanonical beclin-1-independent pathway and was sustained by an astrocytic phosphoprotein (PEA-15) and protein kinase C zeta interactome. Lower levels of tumoral PRL/PRLR in clinical samples were associated with longer patient survival. Our findings provide an understanding of the mechanisms of tumor growth inhibition through targeting PRL/PRLR and may have clinical implications.

Beclin-1

Ovarian Neoplasms - diagnosis

Humans

Spheroids, Cellular - metabolism

Carcinoma - diagnosis

Intracellular Signaling Peptides and Proteins - metabolism

Phosphoproteins - metabolism

Autophagy

Prolactin - pharmacology

Apoptosis Regulatory Proteins - metabolism

Receptors, Prolactin - metabolism

Prolactin - metabolism

Protein Kinase C - metabolism

Cell Death

Biomarkers, Tumor - metabolism

Cell Line, Tumor

Prolactin - antagonists & inhibitors

Female

Membrane Proteins - metabolism

Ovarian Neoplasms - metabolism

Spheroids, Cellular - drug effects

Carcinoma - metabolism

Details

Title: Subtitle: Antagonism of tumoral prolactin receptor promotes autophagy-related cell death
Creators: Yunfei Wen - Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Behrouz Zand - Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Bulent Ozpolat - Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Miroslaw J Szczepanski - Department of Otolaryngology, Medical University of Warsaw, Warsaw 02-091, Poland
Chunhua Lu - Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Erkan Yuca - Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Amy R Carroll - Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Neslihan Alpay - Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Chandra Bartholomeusz - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Ibrahim Tekedereli - Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Yu Kang - Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Rajesha Rupaimoole - Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Chad V Pecot - Department of Thoracic, Head and Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Heather J Dalton - Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Anadulce Hernandez - Department of Biology and Biochemistry, University of Houston, Houston, TX 77024, USA
Anna Lokshin - Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Susan K Lutgendorf - Departments of Psychology and Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Jinsong Liu - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Walter N Hittelman - Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Wen Y Chen - Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA
Gabriel Lopez-Berestein - Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Marta Szajnik - Department of Gynecologic Oncology, Poznan University of Medical Sciences, Poznan 60-535, Poland
Naoto T Ueno - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Robert L Coleman - Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Anil K Sood - Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: asood@mdanderson.org
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.7(2), pp.488-500
DOI: 10.1016/j.celrep.2014.03.009
PMID: 24703838
PMCID: PMC4038960
NLM abbreviation: Cell Rep
ISSN: 2211-1247
eISSN: 2211-1247
Publisher: United States
Grant note: RC2GM092599 / NIGMS NIH HHS CA16672 / NCI NIH HHS CA177909 / NCI NIH HHS R01 CA177909 / NCI NIH HHS P50CA083639 / NCI NIH HHS P50 CA098258 / NCI NIH HHS R01 CA109298 / NCI NIH HHS RC2 GM092599 / NIGMS NIH HHS CA109298 / NCI NIH HHS P30 CA086862 / NCI NIH HHS UH2TR000943 / NCATS NIH HHS 5 P50CA116199 / NCI NIH HHS R01 CA140933 / NCI NIH HHS CA140933 / NCI NIH HHS T32CA101642 / NCI NIH HHS P30 CA016672 / NCI NIH HHS U54CA151668 / NCI NIH HHS P50 CA116199 / NCI NIH HHS U54 CA151668 / NCI NIH HHS P50 CA083639 / NCI NIH HHS P50CA098258 / NCI NIH HHS
Language: English
Date published: 04/24/2014
Academic Unit: Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
Record Identifier: 9984002462402771

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