Orai3 calcium channel and resistance to chemotherapy in breast cancer cells: the p53 connection - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cell Death and Differentiation Année : 2018

Orai3 calcium channel and resistance to chemotherapy in breast cancer cells: the p53 connection

, (1) , , , , , (1) , (1)
1
Jessy Hasna
  • Fonction : Auteur
Lise Rodat-Despoix
Dirk Geerts
  • Fonction : Auteur
Catherine Leroy
  • Fonction : Auteur
David Tulasne
  • Fonction : Auteur

Résumé

Orai proteins are highly selective calcium channels playing an important role in calcium entry. Orai3 channels are overexpressed in breast cancer (BC) tissues, and involved in their proliferation, cell cycle progression and survival. Herein, we sought to address the involvement of Orai3 in resistance to chemotherapeutic drugs. Using high-throughput approaches, we investigated major changes induced by Orai3 overexpression, including downstream signaling mechanisms involved in BC chemotherapy resistance. Resistance was dependent on external calcium presence and thus Orai3 functionality. This effect allowed a downregulation of the p53 tumor suppressor protein expression via the pro-survival PI3K/Sgk-1/Sek-1 pathway. We demonstrated that p53 degradation occurred not only via Mdm2, but also via another unexpected E3 ubiquitin ligase, Nedd4-2. We found supporting bioinformatic evidence linking Orai3 overexpression and chemoresistance in large human BC data sets. Altogether, our results shed light on the molecular mechanisms activated in BC cells commonly found to overexpress Orai3, allowing resistance to chemotherapeutic drugs.

Dates et versions

hal-03607838 , version 1 (14-03-2022)

Identifiants

Citer

Jessy Hasna, Frederic Hague, Lise Rodat-Despoix, Dirk Geerts, Catherine Leroy, et al.. Orai3 calcium channel and resistance to chemotherapy in breast cancer cells: the p53 connection. Cell Death and Differentiation, 2018, 25 (4), pp.691-705. ⟨10.1038/s41418-017-0007-1⟩. ⟨hal-03607838⟩

Collections

U-PICARDIE LPCM
7 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook Twitter LinkedIn More