{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T01:44:07Z","timestamp":1778809447139,"version":"3.51.4"},"reference-count":90,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31571165"],"award-info":[{"award-number":["31571165"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31771288"],"award-info":[{"award-number":["31771288"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Pancreatic cancer is driven by risk factors such as diabetes and chronic pancreatic injury, which are further associated with gut dysbiosis. Intestinal toxins such as bile acids and bacterial endotoxin (LPS), in excess and persistence, can provoke chronic inflammation and tumorigenesis. Of interest is that many intestinal toxins are negatively charged acidic components in essence, which prompted us to test whether oral administration of cationic resin can deplete intestinal toxins and ameliorate pancreatic cancer. Here, we found that increased plasma levels of endotoxin and bile acids in Pdx1-Cre: LSL-KrasG12D\/+ mice were associated with the transformation of the pancreatic ductal carcinoma (PDAC) state. Common bile-duct-ligation or LPS injection impeded autolysosomal flux, leading to Yap accumulation and malignant transformation. Conversely, oral administration of cholestyramine to sequestrate intestinal endotoxin and bile acids resumed autolysosomal flux for Yap degradation and attenuated metastatic incidence. Conversely, chloroquine treatment impaired autolysosomal flux and exacerbated malignance, showing jeopardization of p62\/ Sqxtm1 turnover, leading to Yap accumulation, which is also consistent with overexpression of cystatin A (CSTA) in situ with pancreatic cancer cells and metastatic tumor. At cellular levels, chenodeoxycholic acid or LPS treatment activated the ligand\u2013receptor-mediated AKT-mTOR pathway, resulting in autophagy-lysosomal stress for YAP accumulation and cellular dissemination. Thus, this work indicates a potential new strategy for intervention of pancreatic metastasis through sequestration of intestinal acidic toxins by oral administration of cationic resins.<\/jats:p>","DOI":"10.3390\/cancers14061407","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T02:10:35Z","timestamp":1646878235000},"page":"1407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Sequestration of Intestinal Acidic Toxins by Cationic Resin Attenuates Pancreatic Cancer Progression through Promoting Autophagic Flux for YAP Degradation"],"prefix":"10.3390","volume":"14","author":[{"given":"Guangfu","family":"Zhao","sequence":"first","affiliation":[{"name":"The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu 610017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianci","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu 610017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu 610017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mouad","family":"Edderkaoui","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Los Angeles, CA 90001, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Hu","sequence":"additional","affiliation":[{"name":"Olive View-UCLA Medical Center, Los Angeles, CA 90001, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu 610083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0818-6017","authenticated-orcid":false,"given":"Stephen J.","family":"Pandol","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Los Angeles, CA 90001, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangsheng","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu 610083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6282-7319","authenticated-orcid":false,"given":"Yuan-Ping","family":"Han","sequence":"additional","affiliation":[{"name":"The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu 610017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16022","DOI":"10.1038\/nrdp.2016.22","article-title":"Pancreatic cancer","volume":"2","author":"Kleeff","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"375","DOI":"10.3322\/caac.21626","article-title":"Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma","volume":"70","author":"Grossberg","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5947","DOI":"10.1073\/pnas.0601273103","article-title":"Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse","volume":"103","author":"Bardeesy","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.ccr.2005.04.023","article-title":"Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice","volume":"7","author":"Hingorani","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1172\/JCI59743","article-title":"An NF-\u03baB pathway-mediated positive feedback loop amplifies Ras activity to pathological levels in mice","volume":"122","author":"Daniluk","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/00000478-199802000-00003","article-title":"Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas","volume":"22","author":"Brat","year":"1998","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1097\/01.MP.0000087422.24733.62","article-title":"Clinicopathological correlates of pancreatic intraepithelial neoplasia: A comparative analysis of 82 cases with and 152 cases without pancreatic ductal adenocarcinoma","volume":"16","author":"Andea","year":"2003","journal-title":"Modern Pathol."},{"key":"ref_8","first-page":"2969","article-title":"Progression model for pancreatic cancer","volume":"6","author":"Hruban","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41575-019-0242-7","article-title":"Microbiota in pancreatic health and disease: The next frontier in microbiome research","volume":"17","author":"Thomas","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cell.2014.03.011","article-title":"Role of the microbiota in immunity and inflammation","volume":"157","author":"Belkaid","year":"2014","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1158\/1940-6207.CAPR-16-0249","article-title":"The Human Microbiome and Cancer","volume":"10","author":"Rajagopala","year":"2017","journal-title":"Cancer Prev. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1158\/2159-8290.CD-17-1134","article-title":"The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression","volume":"8","author":"Pushalkar","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/s12967-021-02882-7","article-title":"The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing","volume":"19","author":"Zhou","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/s41401-020-00532-0","article-title":"Gut microbiota in pancreatic diseases: Possible new therapeutic strategies","volume":"42","author":"Pan","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40348-021-00126-8","article-title":"Bacterial metabolites and cardiovascular risk in children with chronic kidney disease","volume":"8","author":"Schlender","year":"2021","journal-title":"Mol. Cell. Pediatrics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.1210\/jc.2015-2518","article-title":"Postprandial Endotoxemia Linked With Chylomicrons and Lipopolysaccharides Handling in Obese Versus Lean Men: A Lipid Dose-Effect Trial","volume":"100","author":"Vors","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1172\/JCI128521","article-title":"The gut-bone axis: How bacterial metabolites bridge the distance","volume":"129","author":"Zaiss","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/s41416-020-01029-7","article-title":"Bacterial lipopolysaccharide as negative predictor of gemcitabine efficacy in advanced pancreatic cancer-translational results from the AIO-PK0104 Phase 3 study","volume":"123","author":"Guenther","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.pan.2018.03.005","article-title":"Characterization of the duodenal bacterial microbiota in patients with pancreatic head cancer vs. healthy controls","volume":"18","author":"Mei","year":"2018","journal-title":"Pancreatology."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ccr.2007.01.012","article-title":"Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice","volume":"11","author":"Guerra","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S87","DOI":"10.5604\/01.3001.0010.5501","article-title":"Bile Acids and Cancer: Direct and Environmental-Dependent Effects","volume":"16","author":"Wang","year":"2017","journal-title":"Ann. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"33265","DOI":"10.18632\/oncotarget.16633","article-title":"Correlated high expression of FXR and Sp1 in cancer cells confers a poor prognosis for pancreatic cancer: A study based on TCGA and tissue microarray","volume":"8","author":"Hu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"188583","DOI":"10.1016\/j.bbcan.2021.188583","article-title":"Matrix stiffness and its influence on pancreatic diseases","volume":"1876","author":"Zhang","year":"2021","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e20210836","DOI":"10.1084\/jem.20210836","article-title":"An NR2F1-specific agonist suppresses metastasis by inducing cancer cell dormancy","volume":"219","author":"Khalil","year":"2022","journal-title":"J. Exp. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/ncb3157","article-title":"Matrix stiffness drives epithelial-mesenchymal transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway","volume":"17","author":"Wei","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e352","DOI":"10.1038\/oncsis.2017.54","article-title":"Matrix stiffness induces epithelial-mesenchymal transition and promotes chemoresistance in pancreatic cancer cells","volume":"6","author":"Rice","year":"2017","journal-title":"Oncogenesis"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1053\/j.gastro.2007.06.062","article-title":"Bacterial endotoxin: A trigger factor for alcoholic pancreatitis? Evidence from a novel, physiologically relevant animal model","volume":"133","author":"Vonlaufen","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1084\/jem.20142162","article-title":"TLR9 ligation in pancreatic stellate cells promotes tumorigenesis","volume":"212","author":"Zambirinis","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.ccell.2016.05.005","article-title":"YAP\/TAZ at the Roots of Cancer","volume":"29","author":"Zanconato","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.cell.2014.06.003","article-title":"Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer","volume":"158","author":"Kapoor","year":"2014","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16759","DOI":"10.1038\/srep16759","article-title":"Role of YAP and TAZ in pancreatic ductal adenocarcinoma and in stellate cells associated with cancer and chronic pancreatitis","volume":"5","author":"Morvaridi","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10137","article-title":"Role of YAP\/TAZ in mechanotransduction","volume":"474","author":"Dupont","year":"2011","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S1535-6108(03)00309-X","article-title":"Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse","volume":"4","author":"Hingorani","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Torres, M.P., Rachagani, S., Souchek, J.J., Mallya, K., Johansson, S.L., and Batra, S.K. (2013). Novel pancreatic cancer cell lines derived from genetically engineered mouse models of spontaneous pancreatic adenocarcinoma: Applications in diagnosis and therapy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080580"},{"key":"ref_35","first-page":"1744","article-title":"Screen-detected gallstone disease and risk of liver and pancreatic cancer: The Kailuan Cohort Study","volume":"40","author":"Zhao","year":"2020","journal-title":"Liver Int. Off. J. Int. Assoc. Study Liver"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jsbmb.2017.10.011","article-title":"Comparison of the composition of bile acids in bile of patients with adenocarcinoma of the pancreas and benign disease","volume":"174","author":"Rees","year":"2017","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.2337\/db17-0070","article-title":"Cationic Polystyrene Resolves Nonalcoholic Steatohepatitis, Obesity, and Metabolic Disorders by Promoting Eubiosis of Gut Microbiota and Decreasing Endotoxemia","volume":"66","author":"Zhu","year":"2017","journal-title":"Diabetes"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"G685","DOI":"10.1152\/ajpgi.00021.2020","article-title":"Liver Injury Impaired 25-Hydroxylation of Vitamin D Suppresses Intestinal Paneth Cell defensins, leading to Gut Dysbiosis and Liver Fibrogenesis","volume":"319","author":"Wu","year":"2020","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1053\/j.gastro.2009.01.066","article-title":"TGF-beta receptor inactivation and mutant Kras induce intestinal neoplasms in mice via a beta-catenin-independent pathway","volume":"136","author":"Trobridge","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.canlet.2018.10.024","article-title":"Diet-induced hepatic steatosis activates Ras to promote hepatocarcinogenesis via CPT1\u03b1","volume":"442","author":"Xu","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41392-017-0005-2","article-title":"Yes-associated protein (YAP) in pancreatic cancer: At the epicenter of a targetable signaling network associated with patient survival","volume":"3","author":"Rozengurt","year":"2018","journal-title":"Signal. Transduct. Target. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1111\/jcmm.13526","article-title":"Lipopolysaccharide enhances TGF-beta1 signalling pathway and rat pancreatic fibrosis","volume":"22","author":"Sun","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21817","DOI":"10.1074\/jbc.M110.131714","article-title":"Disruption of lysosome function promotes tumor growth and metastasis in Drosophila","volume":"285","author":"Chi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1111\/cas.13396","article-title":"Clinical features of cystatin A expression in patients with pancreatic ductal adenocarcinoma","volume":"108","author":"Komura","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S0002-9610(88)80729-3","article-title":"Circulating immune complex, endotoxin, and biliary infection in patients with biliary obstruction","volume":"155","author":"Ohshio","year":"1988","journal-title":"Am. J. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11739-011-0653-0","article-title":"Use and indications of cholestyramine and bile acid sequestrants","volume":"8","author":"Scaldaferri","year":"2013","journal-title":"Intern. Emerg. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E167","DOI":"10.1152\/ajpendo.00416.2016","article-title":"Cholestyramine treatment of healthy humans rapidly induces transient hypertriglyceridemia when treatment is initiated","volume":"313","author":"Straniero","year":"2017","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1126\/science.1174447","article-title":"A gene network regulating lysosomal biogenesis and function","volume":"325","author":"Sardiello","year":"2009","journal-title":"Science."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1440-1746.2011.07013.x","article-title":"Epidemiology, risk factors, and the promotion of pancreatic cancer: Role of the stellate cell","volume":"27","author":"Pandol","year":"2012","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ejrad.2018.09.001","article-title":"The use of magnetic resonance elastography in differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma: A preliminary study","volume":"108","author":"Shi","year":"2018","journal-title":"Eur. J. Radiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2147\/HMER.S7394","article-title":"Liver stiffness: A novel parameter for the diagnosis of liver disease","volume":"2","author":"Mueller","year":"2010","journal-title":"Hepat. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1053\/j.gastro.2012.11.037","article-title":"A starring role for stellate cells in the pancreatic cancer microenvironment","volume":"144","author":"Apte","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13046-018-0740-4","article-title":"Inhibiting YAP expression suppresses pancreatic cancer progression by disrupting tumor-stromal interactions","volume":"37","author":"Jiang","year":"2018","journal-title":"J. Exp. Clin. Cancer Res. CR"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/nature05414","article-title":"An obesity-associated gut microbiome with increased capacity for energy harvest","volume":"444","author":"Turnbaugh","year":"2006","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.2337\/db06-1491","article-title":"Metabolic endotoxemia initiates obesity and insulin resistance","volume":"56","author":"Cani","year":"2007","journal-title":"Diabetes"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1111\/dme.12773","article-title":"Household endotoxin exposure and increased risk of diabetes in older adults","volume":"32","author":"Min","year":"2015","journal-title":"Diabet. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3389\/fphys.2016.00498","article-title":"Vitamin D Signaling through Induction of Paneth Cell Defensins Maintains Gut Microbiota and Improves Metabolic Disorders and Hepatic Steatosis in Animal Models","volume":"7","author":"Su","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.1158\/0008-5472.CAN-16-0294","article-title":"Impact of Pattern Recognition Receptors on the Prognosis of Breast Cancer Patients Undergoing Adjuvant Chemotherapy","volume":"76","author":"Vacchelli","year":"2016","journal-title":"Cancer Res."},{"key":"ref_59","first-page":"1","article-title":"Pattern-recognition receptors and gastric cancer","volume":"5","author":"Kaakoush","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"95176","DOI":"10.18632\/oncotarget.18820","article-title":"Gut microbial profile analysis by MiSeq sequencing of pancreatic carcinoma patients in China","volume":"8","author":"Ren","year":"2017","journal-title":"Oncotarget"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.bbrc.2018.10.169","article-title":"Possible involvement of Enterococcus infection in the pathogenesis of chronic pancreatitis and cancer","volume":"506","author":"Maekawa","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_62","first-page":"3605","article-title":"Association of disease condition with changes in intestinal flora, and plasma endotoxin and vascular endothelial growth factor levels in patients with liver cancer","volume":"24","author":"Jiang","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1002\/jso.21392","article-title":"Lipopolysaccharide (LPS) increases the invasive ability of pancreatic cancer cells through the TLR4\/MyD88 signaling pathway","volume":"100","author":"Ikebe","year":"2009","journal-title":"J. Surg. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1093\/carcin\/bgy073","article-title":"Intestinal microbiota enhances pancreatic carcinogenesis in preclinical models","volume":"39","author":"Thomas","year":"2018","journal-title":"Carcinogenesis"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jss.2006.04.025","article-title":"Bile-reflux into the pancreatic ducts is associated with the development of intraductal papillary carcinoma in hamsters","volume":"136","author":"Adachi","year":"2006","journal-title":"J. Surg. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.molonc.2016.04.007","article-title":"Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer","volume":"10","author":"Joshi","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1002\/ijc.30219","article-title":"Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis","volume":"139","author":"Xie","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_68","first-page":"3567","article-title":"High expression of TGR5 predicts a poor prognosis in patients with pancreatic cancer","volume":"11","author":"Zhao","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1053\/j.gastro.2009.10.052","article-title":"Biliary acute pancreatitis in mice is mediated by the G-protein-coupled cell surface bile acid receptor Gpbar1","volume":"138","author":"Perides","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"17027","DOI":"10.1038\/cddiscovery.2017.27","article-title":"The bile acid receptor FXR attenuates acinar cell autophagy in chronic pancreatitis","volume":"3","author":"Zhou","year":"2017","journal-title":"Cell Death Discov."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.18632\/oncotarget.384","article-title":"Targeting autophagy addiction in cancer","volume":"2","author":"Mancias","year":"2011","journal-title":"Oncotarget"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e2520","DOI":"10.1038\/cddis.2016.415","article-title":"Autophagy and epithelial-mesenchymal transition: An intricate interplay in cancer","volume":"7","author":"Gugnoni","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1101\/gad.283416.116","article-title":"Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cells","volume":"30","author":"Guo","year":"2016","journal-title":"Genes Dev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1091\/mbc.e10-06-0500","article-title":"Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation","volume":"22","author":"Lock","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1101\/gad.2016311","article-title":"Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis","volume":"25","author":"Guo","year":"2011","journal-title":"Genes Dev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1101\/gad.519709","article-title":"Autophagy mediates the mitotic senescence transition","volume":"23","author":"Young","year":"2009","journal-title":"Genes Dev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.molcel.2011.02.009","article-title":"Oncogenic Ras-induced expression of Noxa and Beclin-1 promotes autophagic cell death and limits clonogenic survival","volume":"42","author":"Elgendy","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1001\/jamaoncol.2019.0684","article-title":"Effect of Gemcitabine and nab-Paclitaxel With or Without Hydroxychloroquine on Patients With Advanced Pancreatic Cancer: A Phase 2 Randomized Clinical Trial","volume":"5","author":"Karasic","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1634\/theoncologist.2014-0086","article-title":"Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma","volume":"19","author":"Wolpin","year":"2014","journal-title":"Oncologist"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.3748\/wjg.v27.i23.3158","article-title":"Pancreatic adenocarcinoma: A review of recent paradigms and advances in epidemiology, clinical diagnosis and management","volume":"27","author":"Gupta","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/s41586-019-0885-0","article-title":"Autophagic cell death restricts chromosomal instability during replicative crisis","volume":"565","author":"Nassour","year":"2019","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1146\/annurev-pharmtox-010715-103101","article-title":"Critical Functions of the Lysosome in Cancer Biology","volume":"57","author":"Davidson","year":"2017","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1038\/onc.2009.466","article-title":"Deficiency for the cysteine protease cathepsin L promotes tumor progression in mouse epidermis","volume":"29","author":"Dennemarker","year":"2010","journal-title":"Oncogene"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/978-1-4757-9613-1_34","article-title":"Expression of cysteine protease inhibitors stefin A, stefin B, and cystatin C in human lung tumor tissue","volume":"421","author":"Ebert","year":"1997","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_85","first-page":"432","article-title":"Cysteine proteinase inhibitor cystatin A in breast cancer","volume":"58","author":"Kuopio","year":"1998","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/45257","article-title":"Induction of autophagy and inhibition of tumorigenesis by beclin 1","volume":"402","author":"Liang","year":"1999","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1053\/j.gastro.2018.09.053","article-title":"Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice","volume":"156","author":"Diakopoulos","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1101\/gad.1602907","article-title":"Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control","volume":"21","author":"Zhao","year":"2007","journal-title":"Genes Dev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4962","DOI":"10.1038\/s41467-018-07338-z","article-title":"Autophagy is a gatekeeper of hepatic differentiation and carcinogenesis by controlling the degradation of Yap","volume":"9","author":"Lee","year":"2018","journal-title":"Nature Commun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41419-019-1664-4","article-title":"Activation of Aurora A kinase increases YAP stability via blockage of autophagy","volume":"10","author":"Wang","year":"2019","journal-title":"Cell Death Dis."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/6\/1407\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:34:01Z","timestamp":1760135641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/6\/1407"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,10]]},"references-count":90,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["cancers14061407"],"URL":"https:\/\/doi.org\/10.3390\/cancers14061407","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,10]]}}}