Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance

Shu Chen Liu, Ngan Ming Tsang, Wen Che Chiang, Kai Ping Chang, Chuen Hsueh, Ying Liang, Jyh Lyh Juang, Kai Ping N. Chow, Yu Sun Chang

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

Radioresistance of EBV-associated nasopharyngeal carcinoma (NPC) is associated with poor prognosis for patients with this form of cancer. Here, we found that NPC patients had increased serum levels of leukemia inhibitory factor (LIF) and that higher LIF levels correlated with local tumor recurrence. Furthermore, in vitro studies with NPC cells and in vivo xenograft mouse studies demonstrated that LIF critically contributes to NPC tumor growth and radioresistance. Using these model systems, we found that LIF treatment activated the mTORC1/p70S6K signaling pathway, enhanced tumor growth, inhibited DNA damage responses, and enhanced radioresistance. Treatment with either soluble LIF receptor (sLIFR), a LIF antagonist, or the mTOR inhibitor rapamycin reversed LIF-mediated effects, resulting in growth arrest and increased sensitivity to γ irradiation. Immunohistochemical (IHC) analyses of human NPC biopsies revealed that LIF and LIFR were overexpressed in tumor cells and that LIF expression correlated with the presence of the activated p-p70S6K. Finally, we found that the EBV-encoded protein latent membrane protein 1 (LMP1) enhances LIF production. Together, our findings indicate that LIF promotes NPC tumorigenesis and suggest that serum LIF levels may predict local recurrence and radiosensitivity in NPC patients.

Original languageEnglish
Pages (from-to)5269-5283
Number of pages15
JournalJournal of Clinical Investigation
Volume123
Issue number12
DOIs
StatePublished - 2 Dec 2013

Fingerprint

Dive into the research topics of 'Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance'. Together they form a unique fingerprint.

Cite this