LiBang Yang, Thomas Kono, Adam Gilbertsen, Yingming Li, Bo Sun, Blake A Jacobson, Sabine Karam, Scott M Dehm, Craig A Henke, Robert A Kratzke
{"title":"GPR81核运输对肺癌和其他实体癌的生长和进展至关重要。","authors":"LiBang Yang, Thomas Kono, Adam Gilbertsen, Yingming Li, Bo Sun, Blake A Jacobson, Sabine Karam, Scott M Dehm, Craig A Henke, Robert A Kratzke","doi":"10.5306/wjco.v16.i8.107208","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The Warburg effect is common in cancers. Lactate and its receptor GPR81 play an important role in cancer progression. It is widely accepted that membrane receptor nuclear translocation plays some novel role in cancer pathology. The mechanism by which the lactate/GPR81 axis regulates cancer malignancy remains unclear.</p><p><strong>Aim: </strong>To elucidate the mechanism of GPR81 nuclear transportation promoted by exogenous lactate.</p><p><strong>Methods: </strong>Lung cancer cells were stimulated with exogenous lactate and GPR81 levels were measured by immunofluoresence and western blot analysis in membrane, cytoplasmic, and nuclear fractions. Lung cancer cells were transduced with a mutant GPR81 nuclear localization signal (NLS) construct, wild type GPR81 or empty vector and used to examine how GPR81 nuclear transportation affects lung cancer cells malignancy <i>in vitro</i> and <i>in vivo</i>. Immunoprecipitation Proteomics analysis and Chromatin immunoprecipitation (ChIP) sequencing were used to determine GPR81 interacting proteins and genes.</p><p><strong>Results: </strong>In response to hypoxia/Lactate stimulation, GPR81 translocates and accumulates in the nucleus of lung cancer cells. Functionally, GPR81 nuclear translocation promotes cancer cell proliferation and motility. Depletion of the GPR81 NLS depletes GPR81 nuclear levels and decreases cancer cell growth and invasion <i>in vitro</i>, as well as cancer cell malignancy <i>in vivo.</i> Proteomics analysis revealed a set of proteins including SFPQ, that interact with GPR81 in the cancer cell nucleus. Notably, the interaction of GPR81 with SFPQ promotes cancer cell growth and motility. ChIP sequencing analysis discovered that there is a set of genes targeted by GPR81.</p><p><strong>Conclusion: </strong>The interaction of GPR81 with SFPQ promotes cancer cell malignancy. GPR81 nuclear translocation is critical in conferring cancer progression and may be a potential therapeutic target for limiting cancer progression<b>.</b></p>","PeriodicalId":23802,"journal":{"name":"World journal of clinical oncology","volume":"16 8","pages":"107208"},"PeriodicalIF":3.2000,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400187/pdf/","citationCount":"0","resultStr":"{\"title\":\"GPR81 nuclear transportation is critical for cancer growth and progression in lung and other solid cancers.\",\"authors\":\"LiBang Yang, Thomas Kono, Adam Gilbertsen, Yingming Li, Bo Sun, Blake A Jacobson, Sabine Karam, Scott M Dehm, Craig A Henke, Robert A Kratzke\",\"doi\":\"10.5306/wjco.v16.i8.107208\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The Warburg effect is common in cancers. Lactate and its receptor GPR81 play an important role in cancer progression. It is widely accepted that membrane receptor nuclear translocation plays some novel role in cancer pathology. The mechanism by which the lactate/GPR81 axis regulates cancer malignancy remains unclear.</p><p><strong>Aim: </strong>To elucidate the mechanism of GPR81 nuclear transportation promoted by exogenous lactate.</p><p><strong>Methods: </strong>Lung cancer cells were stimulated with exogenous lactate and GPR81 levels were measured by immunofluoresence and western blot analysis in membrane, cytoplasmic, and nuclear fractions. Lung cancer cells were transduced with a mutant GPR81 nuclear localization signal (NLS) construct, wild type GPR81 or empty vector and used to examine how GPR81 nuclear transportation affects lung cancer cells malignancy <i>in vitro</i> and <i>in vivo</i>. Immunoprecipitation Proteomics analysis and Chromatin immunoprecipitation (ChIP) sequencing were used to determine GPR81 interacting proteins and genes.</p><p><strong>Results: </strong>In response to hypoxia/Lactate stimulation, GPR81 translocates and accumulates in the nucleus of lung cancer cells. Functionally, GPR81 nuclear translocation promotes cancer cell proliferation and motility. Depletion of the GPR81 NLS depletes GPR81 nuclear levels and decreases cancer cell growth and invasion <i>in vitro</i>, as well as cancer cell malignancy <i>in vivo.</i> Proteomics analysis revealed a set of proteins including SFPQ, that interact with GPR81 in the cancer cell nucleus. Notably, the interaction of GPR81 with SFPQ promotes cancer cell growth and motility. ChIP sequencing analysis discovered that there is a set of genes targeted by GPR81.</p><p><strong>Conclusion: </strong>The interaction of GPR81 with SFPQ promotes cancer cell malignancy. GPR81 nuclear translocation is critical in conferring cancer progression and may be a potential therapeutic target for limiting cancer progression<b>.</b></p>\",\"PeriodicalId\":23802,\"journal\":{\"name\":\"World journal of clinical oncology\",\"volume\":\"16 8\",\"pages\":\"107208\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-08-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400187/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World journal of clinical oncology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5306/wjco.v16.i8.107208\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World journal of clinical oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5306/wjco.v16.i8.107208","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
GPR81 nuclear transportation is critical for cancer growth and progression in lung and other solid cancers.
Background: The Warburg effect is common in cancers. Lactate and its receptor GPR81 play an important role in cancer progression. It is widely accepted that membrane receptor nuclear translocation plays some novel role in cancer pathology. The mechanism by which the lactate/GPR81 axis regulates cancer malignancy remains unclear.
Aim: To elucidate the mechanism of GPR81 nuclear transportation promoted by exogenous lactate.
Methods: Lung cancer cells were stimulated with exogenous lactate and GPR81 levels were measured by immunofluoresence and western blot analysis in membrane, cytoplasmic, and nuclear fractions. Lung cancer cells were transduced with a mutant GPR81 nuclear localization signal (NLS) construct, wild type GPR81 or empty vector and used to examine how GPR81 nuclear transportation affects lung cancer cells malignancy in vitro and in vivo. Immunoprecipitation Proteomics analysis and Chromatin immunoprecipitation (ChIP) sequencing were used to determine GPR81 interacting proteins and genes.
Results: In response to hypoxia/Lactate stimulation, GPR81 translocates and accumulates in the nucleus of lung cancer cells. Functionally, GPR81 nuclear translocation promotes cancer cell proliferation and motility. Depletion of the GPR81 NLS depletes GPR81 nuclear levels and decreases cancer cell growth and invasion in vitro, as well as cancer cell malignancy in vivo. Proteomics analysis revealed a set of proteins including SFPQ, that interact with GPR81 in the cancer cell nucleus. Notably, the interaction of GPR81 with SFPQ promotes cancer cell growth and motility. ChIP sequencing analysis discovered that there is a set of genes targeted by GPR81.
Conclusion: The interaction of GPR81 with SFPQ promotes cancer cell malignancy. GPR81 nuclear translocation is critical in conferring cancer progression and may be a potential therapeutic target for limiting cancer progression.
期刊介绍:
The WJCO is a high-quality, peer reviewed, open-access journal. The primary task of WJCO is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of oncology. In order to promote productive academic communication, the peer review process for the WJCO is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJCO are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in oncology. Scope: Art of Oncology, Biology of Neoplasia, Breast Cancer, Cancer Prevention and Control, Cancer-Related Complications, Diagnosis in Oncology, Gastrointestinal Cancer, Genetic Testing For Cancer, Gynecologic Cancer, Head and Neck Cancer, Hematologic Malignancy, Lung Cancer, Melanoma, Molecular Oncology, Neurooncology, Palliative and Supportive Care, Pediatric Oncology, Surgical Oncology, Translational Oncology, and Urologic Oncology.