Regulation of DNA damage repair and lipid uptake by CX3CR1 in epithelial ovarian carcinoma

Jia Xie; Hilal Gurler Main; Joelle D Sacks; Goda G Muralidhar; Maria V Barbolina

doi:10.1038/s41389-018-0046-6

Regulation of DNA damage repair and lipid uptake by CX₃CR1 in epithelial ovarian carcinoma

Oncogenesis. 2018 May 1;7(4):37. doi: 10.1038/s41389-018-0046-6.

Authors

Jia Xie¹, Hilal Gurler Main¹, Joelle D Sacks¹, Goda G Muralidhar¹, Maria V Barbolina²

Affiliations

¹ Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL, 60612, USA.
² Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL, 60612, USA. mvb@uic.edu.

Abstract

Failure of currently used cytotoxic chemotherapy is one of the main reasons behind high mortality from metastatic high grade serous ovarian carcinoma. We found that high expression of a receptor for fractalkine (CX₃CR1) significantly correlated with shorter survival of patients with serous ovarian carcinoma treated with cytotoxic DNA damage chemotherapies, and reduction of CX₃CR1 expression resulted in sensitization to several DNA damaging modalities, including x-ray radiation and cisplatin. Here, we show that CX₃CR1 plays a role in double-strand DNA break response and repair by regulating expression of RAD50 by a MYC-dependent mechanism. We demonstrate that downregulation of CX₃CR1 alone and in a combination with irradiation affects peritoneal metastasis in an organ-specific manner; we show that CX₃CR1 regulates lipid uptake which could control omental metastasis. This study identifies CX₃CR1 as a novel potential target for sensitization of ovarian carcinoma to DNA damage therapies and reduction of peritoneal carcinomatosis.