{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:06:27Z","timestamp":1790683587122,"version":"4.1.0"},"reference-count":32,"publisher":"American Physiological Society","issue":"5","license":[{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"content-version":"vor","delay-in-days":185,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["2019\/33\/B\/NZ3\/02578"],"award-info":[{"award-number":["2019\/33\/B\/NZ3\/02578"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["U1U\/P03\/DW\/14.25"],"award-info":[{"award-number":["U1U\/P03\/DW\/14.25"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Glandular pancreatic epithelia of the acinar or ductal phenotype may seem terminally differentiated, but they are characterized by remarkable cell plasticity. Stress-induced trans-differentiation of these cells has been implicated in the mechanisms of carcinogenesis. Current consensus links pancreatic ductal adenocarcinoma with onco-transformation of ductal epithelia, but under the presence of driver mutations in Kras and Trp53, also with trans-differentiation of pancreatic acini. However, we do not know when, in the course of cancer progression, physiological functions are lost by mutant acinar cells, nor can we assess their capacity for the production of pancreatic juice components. Here, we investigated whether two mutations\u2014KrasG12D and Trp53R172H\u2014present simultaneously in acinar cells of KPC mice (model of oncogenesis) influence cytosolic Ca2+ signals. Since Ca2+ signals control the cellular handling of digestive hydrolases, any changes that affect intracellular signaling events and cell bioenergetics might have an impact on the physiology of the pancreas. Our results showed that physiological doses of acetylcholine evoked less regular Ca2+ oscillations in KPC acinar cells compared to the control, whereas responses to supramaximal concentrations were markedly reduced. Menadione elicited Ca2+ signals of different frequencies in KPC cells compared to control cells. Finally, Ca2+ extrusion rates were significantly inhibited in KPC cells, likely due to the lower basal respiration and ATP production. Cumulatively, these findings suggest that driver mutations affect the signaling capacity of pancreatic acinar cells even before the changes in the epithelial cell morphology become apparent.<\/jats:p>","DOI":"10.1093\/function\/zqad035","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T16:25:03Z","timestamp":1688401503000},"source":"Crossref","is-referenced-by-count":9,"title":["Driver Mutations of Pancreatic Cancer Affect Ca2+ Signaling and ATP Production"],"prefix":"10.1152","volume":"4","author":[{"given":"Kinga B","family":"Stopa","sequence":"first","affiliation":[{"name":"Malopolska Centre of Biotechnology, Jagiellonian University , ul. Gronostajowa 7A, 30-387 Krak\u00f3w , Poland"},{"name":"Doctoral School of Exact and Biological Sciences, Jagiellonian University , ul. \u0141ojasiewicza 11, 30-348 Krak\u00f3w , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"\u0141ozi\u0144ski","sequence":"additional","affiliation":[{"name":"Malopolska Centre of Biotechnology, Jagiellonian University , ul. Gronostajowa 7A, 30-387 Krak\u00f3w , Poland"},{"name":"Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , ul. Gronostajowa 7, 30-387 Krak\u00f3w , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka A","family":"Kusiak","sequence":"additional","affiliation":[{"name":"Doctoral School of Exact and Biological Sciences, Jagiellonian University , ul. \u0141ojasiewicza 11, 30-348 Krak\u00f3w , Poland"},{"name":"Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , ul. Gronostajowa 7, 30-387 Krak\u00f3w , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Litewka","sequence":"additional","affiliation":[{"name":"Doctoral School of Exact and Biological Sciences, Jagiellonian University , ul. \u0141ojasiewicza 11, 30-348 Krak\u00f3w , Poland"},{"name":"Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , ul. Gronostajowa 7, 30-387 Krak\u00f3w , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Krzysztofik","sequence":"additional","affiliation":[{"name":"Malopolska Centre of Biotechnology, Jagiellonian University , ul. Gronostajowa 7A, 30-387 Krak\u00f3w , Poland"},{"name":"Doctoral School of Exact and Biological Sciences, Jagiellonian University , ul. \u0141ojasiewicza 11, 30-348 Krak\u00f3w , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylwester","family":"Mosio\u0142ek","sequence":"additional","affiliation":[{"name":"Malopolska Centre of Biotechnology, Jagiellonian University , ul. Gronostajowa 7A, 30-387 Krak\u00f3w , Poland"},{"name":"Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , ul. Gronostajowa 7, 30-387 Krak\u00f3w , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Morys","sequence":"additional","affiliation":[{"name":"Malopolska Centre of Biotechnology, Jagiellonian University , ul. Gronostajowa 7A, 30-387 Krak\u00f3w , Poland"},{"name":"Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , ul. Gronostajowa 7, 30-387 Krak\u00f3w , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142 E","family":"Ferdek","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , ul. 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