TY  - JOUR
T1  - Mutant KRAS Drives Loss of S100PBP Expression, Enhancing Pancreatic Cancer Progression and Poor Prognosis
A1  - Pedro Henrique Monteiro
A1  - Lucas André Ferreira
JF  - Archive of International Journal of Cancer and Allied Science
JO  - Arch Int J Cancer Allied Sci
SN  - 3108-4834
Y1  - 2024
VL  - 4
IS  - 2
DO  - 10.51847/FrbLuzb4Yz
SP  - 167
EP  - 185
N2  - Previous research indicated a gradual reduction in the levels of S100P-binding protein (S100PBP) during the progression of pancreatic ductal adenocarcinoma (PDAC). In this study, we show that the loss of S100PBP contributes to the transformation of pancreatic cells into oncogenic forms. Both computational and laboratory analyses revealed that deregulation of S100PBP expression impacts several genes involved in the regulation of the cytoskeleton, cell movement, and survival. Overexpression of S100P suppressed S100PBP levels, and co-immunoprecipitation experiments suggested that S100P interacts with the S100PBP-p53-ubiquitin complex, potentially leading to its degradation. Activation of KrasG12D with doxycycline resulted in lower S100PBP levels, which were restored by treating with the HDAC inhibitor MS-275 in both human and murine PDAC cell lines. This suggests KrasG12D regulates S100PBP at an epigenetic level. Additionally, TCGA PanCancer Atlas PDAC datasets showed that low levels of S100PBP and high levels of S100P correlate with poor prognosis in patients, positioning S100PBP as a potential tumor suppressor with clinical relevance.
UR  - https://smerpub.com/article/mutant-kras-drives-loss-of-s100pbp-expression-enhancing-pancreatic-cancer-progression-and-poor-prog-wfwzxnqsbzq20rk
ER  -