TY - JOUR
T1 - Protein kinase D1 — A targetable mediator of pancreatic cancer development
AU - Fleming Martinez, Alicia K.
AU - Storz, Peter
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2024/2
Y1 - 2024/2
N2 - Members of the Protein kinase D (PKD) kinase family each play important cell-specific roles in the regulation of normal pancreas functions. In pancreatic diseases PKD1 is the most widely characterized isoform with roles in pancreatitis and in induction of pancreatic cancer and its progression. PKD1 expression and activation increases in pancreatic acinar cells through macrophage secreted factors, Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling, and reactive oxygen species (ROS), driving the formation of precancerous lesions. In precancerous lesions PKD1 regulates cell survival, growth, senescence, and generation of doublecortin like kinase 1 (DCLK1)-positive cancer stem cells (CSCs). Within tumors, regulation by PKD1 includes chemoresistance, apoptosis, proliferation, CSC features, and the Warburg effect. Thus, PKD1 plays a critical role throughout pancreatic disease initiation and progression.
AB - Members of the Protein kinase D (PKD) kinase family each play important cell-specific roles in the regulation of normal pancreas functions. In pancreatic diseases PKD1 is the most widely characterized isoform with roles in pancreatitis and in induction of pancreatic cancer and its progression. PKD1 expression and activation increases in pancreatic acinar cells through macrophage secreted factors, Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling, and reactive oxygen species (ROS), driving the formation of precancerous lesions. In precancerous lesions PKD1 regulates cell survival, growth, senescence, and generation of doublecortin like kinase 1 (DCLK1)-positive cancer stem cells (CSCs). Within tumors, regulation by PKD1 includes chemoresistance, apoptosis, proliferation, CSC features, and the Warburg effect. Thus, PKD1 plays a critical role throughout pancreatic disease initiation and progression.
KW - Pancreatic cancer
KW - Pancreatic ductal adenocarcinoma
KW - Pancreatic expression
KW - Pancreatitis
KW - PKD
KW - Precancerous lesions
KW - Progression
KW - Protein kinase D
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U2 - 10.1016/j.bbamcr.2023.119646
DO - 10.1016/j.bbamcr.2023.119646
M3 - Review article
C2 - 38061566
AN - SCOPUS:85179085102
SN - 0167-4889
VL - 1871
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
IS - 2
M1 - 119646
ER -