Alteration of cathepsin D trafficking induced by hypoxia and extracellular acidification in MCF-7 breast cancer cells

Abstract : The microenvironment that surrounds tumor cells is characterized by hypoxic conditions and extracellular acidity. These hostile conditions induce crucial changes in cell behavior and can promote the secretion of many soluble factors such as growth factors, cytokines and enzymes. The lysosomal aspartyl-endopeptidase cathepsin D (CD) is a marker of poor prognosis in breast cancer and is associated with a metastatic risk. In this study, the transport of CD was investigated in a model of breast cancer cells line (MCF-7) cultivated under hypoxia and acidification of media. CD secretion was assessed using Western blot analysis and protease activity was measured in conditioned culture media. We demonstrate that cultured MCF-7 cells secrete an active 52 kDa pCD precursor and report that under hypoxia there was an increased amount of pCD secreted. More surprisingly, extracellular acidification (pH 6 and 5.6) induced the secretion of the fully-mature and active (34 kDa + 14 kDa) double chain CD. Our findings reflect the fact that chemical anomalies influence the secretion path of CD in a breast cancer cell model, resulting in altered trafficking of the mature form. This important result may provide new arguments in favor of the role of extracellular CD in the degradation of the matrix proteins that constitute the breast tumor microenvironment.
Type de document :
Article dans une revue
Biochimie, Elsevier, 2016, 121, pp.123 - 130. 〈10.1016/j.biochi.2015.11.007〉
Liste complète des métadonnées

https://hal.archives-ouvertes.fr/hal-01405335
Contributeur : Isabelle Frapart <>
Soumis le : mardi 29 novembre 2016 - 17:43:03
Dernière modification le : mardi 10 octobre 2017 - 16:20:12

Identifiants

Citation

Oussama Achour, Yahya Ashraf, Nicolas Bridiau, Meriem Kacem, Nicolas Poupard, et al.. Alteration of cathepsin D trafficking induced by hypoxia and extracellular acidification in MCF-7 breast cancer cells. Biochimie, Elsevier, 2016, 121, pp.123 - 130. 〈10.1016/j.biochi.2015.11.007〉. 〈hal-01405335〉

Partager

Métriques

Consultations de la notice

78