[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-384178-105":59,"doc-detail-384178-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","sigma1-regulates-lipid-dropletmediated-redox-homeostasis-required-for-prostate-cancer-proliferation","Sigma1 Regulates Lipid Droplet–Mediated Redox Homeostasis Required for Prostate Cancer Proliferation","","Lipid droplets (LD) operate as dynamic hubs for cellular metabolism and also help maintain redox homeostasis, buffering lipid oxidative stress. In prostate cancer, androgen receptor (AR) signaling promotes lipid droplet biogenesis and coordinated oxidative stress control to support proliferation. The study identifies Sigma1/SIGMAR as a ligand-operated scaffolding regulator of LD metabolism. Sigma1 inhibition induces lipophagy to limit LD accumulation that normally sequesters reactive oxygen species (ROS), disrupting LD-autophagy-redox buffering interplay and suppressing proliferation in vitro and tumor growth in vivo. SIGMAR transcripts strongly associate with lipid metabolism and ROS pathways in patient tumors.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/sigma1-regulates-lipid-dropletmediated-redox-homeostasis-required-for-prostate-cancer-proliferation/384178/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/sigma1-regulates-lipid-dropletmediated-redox-homeostasis-required-for-prostate-cancer-proliferation/384178.png","ImageObject",300,407,{"name":92,"@type":93},"McGucket","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",15,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What role do lipid droplets play in redox homeostasis according to the study?","Question",{"text":113,"@type":114},"Lipid droplets function as hubs for metabolism and help maintain redox homeostasis by buffering oxidative lipid stress. They also sequester toxic lipid species and reactive oxygen species (ROS).","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does Sigma1 inhibition affect prostate cancer cell proliferation?",{"text":118,"@type":114},"Sigma1 inhibition triggers lipophagy, a lipid droplet–selective autophagy, preventing LD accumulation. This disrupts LD-mediated buffering of oxidative stress and redox homeostasis, suppressing proliferation in vitro and tumor growth in vivo.",{"name":120,"@type":111,"acceptedAnswer":121},"What clinical relevance is suggested by SIGMAR transcripts in prostate tumors?",{"text":122,"@type":114},"SIGMAR transcripts are reported to be strongly associated with lipid metabolism and ROS pathways in prostate tumors, consistent with the experimental findings.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},384178,1790701435,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":36},1236954412713,"https://us-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","RESEARCH ARTICLE  [https://doi.org/10.1158/2767-9764.CRC-22-0371](https://doi.org/10.1158/2767-9764.CRC-22-0371)  OPEN ACCESS  \nSigma1 Regulates Lipid Droplet–Mediated Check for  \nupdates  \nRedox Homeostasis Required for Prostate Cancer Proliferation  \nHalley M. Oyer1 , 2 , Alexandra R. Steck1 , 2 , Charles G. Longen1 , 2 , Sanjana Venkat1 , 2 , Konuralp Bayrak1 , 2 , Eleanor B. Munger3 , Dan Fu3 , Paola A. Castagnino1 , 2 , Christina M. Sanders1 , 2 , Nathalia A. Tancler1 , 2 , My T. Mai1 , 2 , Justin P. Myers1 , 2 , Matthew J. Schiewer1 , 2 , 4 , Nan Chen1 , 2 , Elahe A. Mostaghel5 , 6 , and Felix J. Kim1 , 2  \nABSTRACT  \nLipid droplets (LD) are dynamic organelles that serve as hubs of cellular metabolic processes. Emerging evidence shows that LDs also play a critical role in maintaining redox homeostasis and can mitigate lipid oxidative stress. In multiple cancers, including prostate cancer, LD accumulation is associated with cancer aggressiveness, therapy resistance, and poor clinical outcome. Prostate cancer arises as an androgen receptor (AR)-driven disease. Among its myriad roles, AR mediates the biosynthesis of LDs, induces autophagy, and modulates cellular oxidative stress in a tightly regulated cycle that promotes cell proliferation. The factors regulating the interplay of these metabolic processes downstream of AR remain unclear. Here, we show that Sigma1/SIGMAR􀀂, a unique ligand-operated scaffolding protein, regulates LD metabolism in prostate cancer cells. Sigma1 inhibition triggers lipophagy, an LD selective form of autophagy, to prevent accumulation of LDs which normally act to sequester toxic levels of reactive oxygen species  \n(ROS). This disrupts the interplay between LDs, autophagy, buffering ofoxidative stress and redox homeostasis, and results in the suppression of cell proliferation in vitro and tumor growth in vivo. Consistent with these experimental results, SIGMAR􀀂 transcripts are strongly associated with lipid metabolism and ROS pathways in prostate tumors. Altogether, these data reveal a novel, pharmacologically responsive role for Sigma1 in regulating the redox homeostasis required by oncogenic metabolic programs that drive prostate cancer proliferation.  \nSignificance: To proliferate, cancer cells must maintain productive metabolic and oxidative stress (eustress) while mitigating destructive, uncontrolled oxidative stress (distress) . LDs are metabolic hubs that enable adaptive responses to promote eustress. Targeting the unique Sigma1 protein can trigger distress by disrupting the LD-mediated homeostasis required for proliferation.  \nIntroduction  \nLipid droplets (LD) are ubiquitous, dynamic organelles that are generated de novo to store and traffic neutral lipids for energy and lipid precursors for mem-  \n1 Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. 2 Sidney Kimmel Cancer Center at Jefferson, Philadelphia, Pennsylvania. 3 Department of Chemistry, University of Washington, Seattle, Washington. 4 Department of Urology, Thomas Jefferson University, Philadelphia, Pennsylvania. 5 Department of Medicine, University of Washington, Seattle, Washington. 6 Geriatric Research, Education and Clinical Center, U.S. Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington.  \nH. M. Oyer and A. R. Steck contributed equally to this article.  \nCorresponding Author: Felix J. Kim, Sidney Kimmel Cancer Center at Jefferson, 233 South 10th St, BLSB 809A, Philadelphia, PA 19107. E-mail:  \n[felix.kim@jefferson.edu](felix.kim@jefferson.edu)  \ndoi: 10.1158/2767-9764 .CRC-22-0371  \nThis open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4 .0) license.  \n© 2023 The Authors; Published by the American Association for Cancer Research  \nbrane biosynthesis and signaling. LDs function as hubs for metabolic processes and are integral to physiologic cell metabolism (1, 2) . LDs also funct","cbCaiotjhc4nxLaj","https://ap.wps.com/l/cbCaiotjhc4nxLaj","pdf",12158827,16,"English","# Abstract\n# Significance\n# Introduction","[{\"question\":\"What role do lipid droplets play in redox homeostasis according to the study?\",\"answer\":\"Lipid droplets function as hubs for metabolism and help maintain redox homeostasis by buffering oxidative lipid stress. They also sequester toxic lipid species and reactive oxygen species (ROS).\"},{\"question\":\"How does Sigma1 inhibition affect prostate cancer cell proliferation?\",\"answer\":\"Sigma1 inhibition triggers lipophagy, a lipid droplet–selective autophagy, preventing LD accumulation. This disrupts LD-mediated buffering of oxidative stress and redox homeostasis, suppressing proliferation in vitro and tumor growth in vivo.\"},{\"question\":\"What clinical relevance is suggested by SIGMAR transcripts in prostate tumors?\",\"answer\":\"SIGMAR transcripts are reported to be strongly associated with lipid metabolism and ROS pathways in prostate tumors, consistent with the experimental findings.\"}]","Sigma1 Regulates Lipid Droplet–Mediated Redox Homeostasis Required for Prostate Cancer Proliferation | PDF",1790261532]