{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:02:54Z","timestamp":1780552974913,"version":"3.54.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005845","name":"Hyogo College of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005845","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["por-journal.com"],"crossmark-restriction":true},"short-container-title":["Pathol. Oncol. Res."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Small intestinal gastrointestinal stromal tumors (SI-GISTs) have a higher risk of distant metastasis and recurrence than gastric GISTs (G-GISTs). However, the underlying mechanisms contributing to the poor prognosis of SI-GISTs remain elusive. Previous research has demonstrated that SI-GISTs exhibit elevated expression of\n                      <jats:italic>Connexin 43<\/jats:italic>\n                      (\n                      <jats:italic>Cx43<\/jats:italic>\n                      ), a component of gap junctions, whereas G-GISTs exhibit minimal expression. The differential expression of\n                      <jats:italic>Cx43<\/jats:italic>\n                      between G-GISTs and SI-GISTs may account for their distinct clinical behavior. This study aimed to investigate the impact of\n                      <jats:italic>Cx43<\/jats:italic>\n                      on the liver metastatic potential of GIST cells, both\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To elucidate the relationship between\n                      <jats:italic>Cx43<\/jats:italic>\n                      expression and poor prognosis in SI-GISTs, we conducted a comparative analysis of original GIST-T1 cells, which express minimal levels of\n                      <jats:italic>Cx43<\/jats:italic>\n                      and represent G-GISTs, and GIST-T1 cells engineered to express high levels of\n                      <jats:italic>Cx43<\/jats:italic>\n                      through transfection with\n                      <jats:italic>Cx43<\/jats:italic>\n                      cDNA (GIST-T1-Cx43 cells), representing SI-GISTs. This was achieved using a newly developed\n                      <jats:italic>in vivo<\/jats:italic>\n                      liver metastasis xenograft mouse model, and the results were corroborated by conventional\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In GIST cells,\n                      <jats:italic>Cx43<\/jats:italic>\n                      enhanced the liver metastatic potential\n                      <jats:italic>in vivo<\/jats:italic>\n                      (p = 0.010).\n                      <jats:italic>In vitro<\/jats:italic>\n                      ,\n                      <jats:italic>Cx43<\/jats:italic>\n                      suppressed cell proliferation (p &amp;lt; 0.001) while promoting migration (p &amp;lt; 0.001), invasion (p = 0.036), tumor-endothelial cell adhesion (p &amp;lt; 0.001), and transendothelial migration (p &amp;lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Elevated\n                      <jats:italic>Cx43<\/jats:italic>\n                      expression may contribute to the poor prognosis of patients with SI-GISTs by enhancing their metastatic potential.\n                      <jats:italic>Cx43<\/jats:italic>\n                      represents a potential novel therapeutic target for the inhibition of SI-GIST metastasis.\n                    <\/jats:p>\n                  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