Role of TMEM45A in physiology and in cancer cell chemoresistance
In collaboration with Profs Y. Poumay, O. De Backer, J. Wouters as well as with Profs C. Graux and L. D’Hondt (CHU UCL Namur) and PhD students (Thomas Dal Maso and Sébastien Marx)
Through a whole genome transcriptomic approach, several candidate genes whose expression is regulated by hypoxia and that may be responsible for cancer cell resistance have been identified in MDA-MB-231 cells exposed to paclitaxel under hypoxia. The invalidation of TMEM45A induced a reversion of the resistance induced by hypoxia. TMEM45A silencing also reverted the protection of HepG2 cells from the etoposide-induced apoptosis under hypoxia
Furthermore, Kaplan Meier survival curves showed an association between high TMEM45A expression and poor prognosis in breast cancer patients. The induction of TMEM45A by hypoxia has been already observed but its potential role in chemoresistance has never been described before. Interestingly, the functions of this protein remain completely unknown. In order to characterize this protein, mice KO for TMEM45A have been generated by our group: there is no effect on fertility and no obvious phenotype. Finally, we have shown that this protein is highly expressed in differentiated keratinocytes but its role in the keratinization process is unclear. The present project aims at further characterizing the functions of TMEM45A in normal physiology as well as in tumor development. Structural studies of the protein for targeting by chemosensibilizing agents are under development.
Selected publications
- Hayez A, Roegiers E, Malaisse J, Balau B, Sterpin C, Achouri Y, Lambert De Rouvroit C, Poumay Y, Michiels C & De Backer O. 2016, ‘TMEM45A Is Dispensable for Epidermal Morphogenesis, Keratinization and Barrier Formation’ PLoS One, vol 11, pp. e0147069.
- Hayez, A, Malaisse, J, Roegiers, E, Reynier, M, Renard, C, Haftek, M, Geenen, V, Serre, G, Simon, M, Lambert de Rouvroit, C, Michiels, C & Poumay, Y 2014, 'High TMEM45A expression is correlated to epidermal keratinization' Experimental Dermatology, vol 23, no. 5, pp. 339-344.
- Flamant, L, Roegiers, E, Pierre, M, Hayez, A, Sterpin, C, De Backer, O, Arnould, T, Poumay, Y & Michiels, C 2012, 'TMEM45A is essential for hypoxia-induced chemoresistance in breast and liver cancer cells' Molecular Cancer, vol 12, no. 1, 391.