RT Journal Article
T1 The mechanism of sitagliptin inhibition of colorectal cancer cell lines' metastatic functionalities
A1 Varela Calviño, Rubén
A1 Rodríguez Quiroga, Marta
A1 Dias Carvalho, Patrícia
A1 Martins, Flavia
A1 Serra-Roma, André
A1 Vázquez Iglesias, Lorena
A1 Páez de la Cadena, María
A1 Velho, Sérgia
A1 Cordero Santamaría, Óscar Javier
K1 CD26
K1 Sitagliptin
K1 Aggregation
K1 Collagen
K1 Colorectal cancer
K1 Dipeptidyl peptidase 4
K1 Invasion
K1 Metastasis
K1 Motility
AB The cell membrane glycoprotein CD26 with peptidase activity (DPP4) and/or its soluble CD26/DPP4 counterpart expression and/or activity are altered in several cancers. Its role in metastasis development was recently highlighted by the discovery of CD26+ cancer stem cell subsets and the fact that clinical DPP4 inhibitors showed antimetastatic effects in animal models. Also, diabetic patients treated with the DPP4 inhibitor sitagliptin showed greater overall survival after colorectal or lung cancer surgery than patients under other diabetic therapies. However, the mechanism of action of these inhibitors in this context is unclear. We studied the role of CD26 and its DPP4 enzymatic activity in malignant cell features such as cell-to-cell homotypic aggregation, cancer cell motility, and invasion in a panel of human colorectal cancer (CRC) cell lines, avoiding models that include the physiological role of DPP4 in chemotaxis. Present results indicate that CD26 participates in the induction of cell invasion, motility, and aggregation of CD26-positive CRC cell lines. Moreover, only invasion and motility assays, which are collagen matrix-dependent, showed a decrease upon treatment with the DPP4 inhibitor sitagliptin. Sitagliptin showed opposite effects to those of transforming growth factor-β1 on epithelial-to-mesenchymal transition and cell cycle, but this result does not explain its CD26/DPP4-dependent effect. These results contribute to the elucidation of the molecular mechanisms behind sitagliptin inhibition of metastatic traits. At the same time, this role of sitagliptin may help to define areas of medicine where DPP4 inhibitors might be introduced. However, they also suggest that additional tools against CD26 as a target might be used or developed for metastasis prevention in addition to gliptins.
PB Wiley ; International Union of Biochemistry and Molecular Biology (IUBMB)
SN 1521-6543
YR 2021
FD 2021
LK https://hdl.handle.net/10347/39267
UL https://hdl.handle.net/10347/39267
LA eng
NO Varela‐Calviño, R., Rodríguez‐Quiroga, M., Dias Carvalho, P., Martins, F., Serra‐Roma, A., Vázquez‐Iglesias, L., ... & Cordero, O. J. (2021). The mechanism of sitagliptin inhibition of colorectal cancer cell lines' metastatic functionalities. IUBMB life, 73(5), 761-773.
NO Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia: a) Axudas consolidación e estructuración de unidade unidades de investigación competitiva, Grant/Award Numbers: (GRC2014/019); b) Galician Network for Colorectal Cancer Research (REGICC), Grant/Award Numbers: ED431D 2017/23; Fundaç~ao para a Ciência e a Tecnologia, Grant/Award Numbers: COMPETE (POCI01-0145-FEDER-016390), NORTE01-0145-FEDER-000029
DS Minerva
RD 24 abr 2026