@article{10.1172/jci.insight.86873, author = {Maria J. Fernández-Cabezudo AND Issam Faour AND Kenneth Jones AND Devin P. Champagne AND Mohammed A. Jaloudi AND Yassir A. Mohamed AND Ghada Bashir AND Saeeda Almarzooqi AND Alia Albawardi AND M. Jawad Hashim AND Thomas S. Roberts AND Haytham El-Salhat AND Hakam El-Taji AND Adnan Kassis AND Dylan E. O’Sullivan AND Brock C. Christensen AND James DeGregori AND Basel K. al-Ramadi AND Mercedes Rincon}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Deficiency of mitochondrial modulator MCJ promotes chemoresistance in breast cancer}, year = {2016}, month = {5}, volume = {1}, url = {https://insight.jci.org/articles/view/86873}, abstract = {Despite major advances in early detection and prognosis, chemotherapy resistance is a major hurdle in the battle against breast cancer. Identifying predictive markers and understanding the mechanisms are key steps to overcoming chemoresistance. Methylation-controlled J protein (MCJ, also known as DNAJC15) is a negative regulator of mitochondrial respiration and has been associated with chemotherapeutic drug sensitivity in cancer cell lines. Here we show, in a retrospective study of a large cohort of breast cancer patients, that low MCJ expression in breast tumors predicts high risk of relapse in patients treated with chemotherapy; however, MCJ expression does not correlate with response to endocrine therapy. In a prospective study in breast cancer patients undergoing neoadjuvant therapy, low MCJ expression also correlates with poor clinical response to chemotherapy and decreased disease-free survival. Using MCJ-deficient mice, we demonstrate that lack of MCJ is sufficient to induce mammary tumor chemoresistance in vivo. Thus, loss of expression of this endogenous mitochondrial modulator in breast cancer promotes the development of chemoresistance.}, number = {7}, doi = {10.1172/jci.insight.86873}, url = {https://doi.org/10.1172/jci.insight.86873}, }