The incidence and mortality rates of gastrointestinal tumors account for 26%and 35%of global malignant tumors,respectively,and continue to rise annually.Elucidating the molecular mechanisms of occurrence and development of gastrointestinal tumors,as well as establishing precise molecularly targeted intervention strategies,have become critical scientific challenges in oncology research.Doublecortin-like kinase 1(DCLK1),a type II transmembrane protein harboring serine/threonine kinase domains,is well-recognized as a specific molecular marker for cancer stem cells.DCLK1 has been demonstrated to directly promote tumor progression by enhancing the autonomous malignant phenotype of tumor cells,while also indirectly driving tumorigenesis through modulation of tumor immune microenvironment.In recent years,tissue-resident memory T cells(TRM),characterized by their sustained tissue residency and potent antitumor immune efficacy,have emerged as a novel avenue for cancer immunotherapy.This article systematically reviews the molecular regulatory mechanisms of DCLK1 in gastrointestinal tumors,with a focus on its potential association with TRM cell functional activation,aiming to provide a theoretical foundation for DCLK1-targeted inhibitors or monoclonal antibody-based immunotherapeutic strategies.

Objective To investigate the effects of doublecortin-like kinase 1(DCLK1)on the malignant biological behaviors,such as proliferation,migration,and invasion,of A549 cell line and their corresponding mechanisms.Methods DCLK1-overexpressing A549 cell lines were established through lentiviral infection,and DCLK1 expression was validated by using RT-PCR and Western blot analysis.Proliferation ability was assessed with CCK-8 and plate cloning assays,and migration and invasion abilities were examined with Transwell assays.The pathway regulated by DCLK1 in lung adenocarcinoma was analyzed on the basis of the TCGA lung adenocarcinoma cohort with pathway enrichment analysis and verified through Western blot analysis.Results DCLK1 overexpression in A549 cells promoted cell proliferation,migration,and invasion.The inhibition of the FAK/PI3K/AKT/mTOR signaling pathway impaired the DCLK1-mediated malignant behavior of A549 cells.Conclusion DCLK1 promotes the malignant behavior of A549 cells through the activation of the FAK/PI3K/AKT/mTOR signaling pathway.

The incidence and mortality rates of gastrointestinal tumors account for 26%and 35%of global malignant tumors,respectively,and continue to rise annually.Elucidating the molecular mechanisms of occurrence and development of gastrointestinal tumors,as well as establishing precise molecularly targeted intervention strategies,have become critical scientific challenges in oncology research.Doublecortin-like kinase 1(DCLK1),a type II transmembrane protein harboring serine/threonine kinase domains,is well-recognized as a specific molecular marker for cancer stem cells.DCLK1 has been demonstrated to directly promote tumor progression by enhancing the autonomous malignant phenotype of tumor cells,while also indirectly driving tumorigenesis through modulation of tumor immune microenvironment.In recent years,tissue-resident memory T cells(TRM),characterized by their sustained tissue residency and potent antitumor immune efficacy,have emerged as a novel avenue for cancer immunotherapy.This article systematically reviews the molecular regulatory mechanisms of DCLK1 in gastrointestinal tumors,with a focus on its potential association with TRM cell functional activation,aiming to provide a theoretical foundation for DCLK1-targeted inhibitors or monoclonal antibody-based immunotherapeutic strategies.