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Article Dans Une Revue Mitochondrion Année : 2022

Cancer/Testis Antigen 55 is required for cancer cell proliferation and mitochondrial DNA maintenance

Jade Aurrière
  • Fonction : Auteur
David Goudenege
  • Fonction : Auteur
Simone Baechler
  • Fonction : Auteur
Shar-Yin Huang
  • Fonction : Auteur
Naig Gueguen
  • Fonction : Auteur
Valerie Desquiret-Dumas
  • Fonction : Auteur
Floris Chabrun
  • Fonction : Auteur
Rodolphe Perrot
  • Fonction : Auteur
Arnaud Chevrollier
Majida Charif
  • Fonction : Auteur
Yves Pommier
  • Fonction : Auteur
Guy Lenaers
Salim Khiati
  • Fonction : Auteur

Résumé

Cancer/Testis Antigens (CTAs) represent a group of proteins whose expression under physiological conditions is restricted to testis but activated in many human cancers. Also, it was observed that co-expression of multiple CTAs worsens the patient prognosis. Five CTAs were reported acting in mitochondria and we recently reported 147 transcripts encoded by 67 CTAs encoding for proteins potentially targeted to mitochondria. Among them, we identified the two isoforms encoded by CT55 for whom the function is poorly understood. First, we found that patients with tumors expressing wild-type CT55 are associated with poor survival. Moreover, CT55 silencing decreases dramatically cell proliferation. Second, to investigate the role of CT55 on mitochondria, we first show that CT55 is localized to both mitochondria and endoplasmic reticulum (ER) due to the presence of an ambiguous N-terminal targeting signal. Then, we show that CT55 silencing decreases mtDNA copy number and delays mtDNA recovery after an acute depletion. Moreover, demethylation of CT55 promotor increases its expression, which in turn increases mtDNA copy number. Finally, we measured the mtDNA copy number in NCI-60 cell lines and screened for genes whose expression is strongly correlated to mtDNA amount. We identified CT55 as the second highest correlated hit. Also, we show that compared to siRNA scrambled control (siCtrl) treatment, CT55 specific siRNA (siCT55) treatment down-regulates aerobic respiration, indicating that CT55 sustains mitochondrial respiration. Altogether, these data show for first time that CT55 acts on mtDNA copy number, modulates mitochondrial activity to sustain cancer cell proliferation.
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Dates et versions

hal-03771509 , version 1 (16-05-2024)

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Jade Aurrière, David Goudenege, Simone Baechler, Shar-Yin Huang, Naig Gueguen, et al.. Cancer/Testis Antigen 55 is required for cancer cell proliferation and mitochondrial DNA maintenance. Mitochondrion, 2022, 64, pp.19-26. ⟨10.1016/j.mito.2022.02.005⟩. ⟨hal-03771509⟩
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