Hess_2024_Biochim.Biophys.Acta.Mol.Basis.Dis__167133

Reference

Title : Dipeptidyl-peptidase 9 regulates the dynamics of tumorigenesis and metastasis in breast cancer - Hess_2024_Biochim.Biophys.Acta.Mol.Basis.Dis__167133
Author(s) : Hess L , Aliar K , Grunwald BT , Griffin R , Lozan A , Knoller M , Khokha R , Brummer T , Reinheckel T
Ref : Biochimica & Biophysica Acta Mol Basis Dis , :167133 , 2024
Abstract : The cytosolic dipeptidyl-aminopeptidase 9 (DPP9) cleaves protein N-termini post-proline or -alanine. Our analysis of DPP9 mRNA expression from the TCGA 'breast cancer' data set revealed that low/intermediate DPP9 levels are associated with poor overall survival of breast cancer patients. To unravel the impact of DPP9 on breast cancer development and progression, the transgenic MMTV-PyMT mouse model of metastasizing breast cancer was used. In addition, tissue- and time-controlled genetic deletion of DPP9 by the Cre-loxP recombination system was done. Despite a delay of tumor onset, a higher number of lung metastases were measured in DPP9-deficient mice compared to controls. In human mammary epithelial cells with oncogenic RAS pathway activation, DPP9 deficiency delayed tumorigenic transformation and accelerated TGF-beta1 induced epithelial-to-mesenchymal transition (EMT) of spheroids. For further analysis of the mechanism, primary breast tumor cells were isolated from the MMTV-PyMT model. DPP9 deficiency in these cells caused cancer cell migration and invasion accompanied by EMT. In absence of DPP9, the EMT transcription factor ZEB1 was stabilized due to insufficient degradation by the proteasome. In summary, low expression of DPP9 appears to decelerate mammary tumorigenesis but favors EMT and metastasis, which establishes DPP9 as a novel dynamic regulator of breast cancer initiation and progression.
ESTHER : Hess_2024_Biochim.Biophys.Acta.Mol.Basis.Dis__167133
PubMedSearch : Hess_2024_Biochim.Biophys.Acta.Mol.Basis.Dis__167133
PubMedID: 38531482
Gene_locus related to this paper: human-DPP9 , mouse-dpp9

Related information

Gene_locus related to this paper: human-DPP9 , mouse-dpp9

Citations formats

Hess L, Aliar K, Grunwald BT, Griffin R, Lozan A, Knoller M, Khokha R, Brummer T, Reinheckel T (2024)
Dipeptidyl-peptidase 9 regulates the dynamics of tumorigenesis and metastasis in breast cancer
Biochimica & Biophysica Acta Mol Basis Dis :167133

Hess L, Aliar K, Grunwald BT, Griffin R, Lozan A, Knoller M, Khokha R, Brummer T, Reinheckel T (2024)
Biochimica & Biophysica Acta Mol Basis Dis :167133