Abstract
High levels of stanniocalcin2 (STC2), a member of the STC secreted glycoprotein family, correlates with tumor progression and poor prognosis. It has been reported that STC2 is over-expressed in response to various stresses, including hypoxia, endoplasmic reticulum stress, oxidative stress and irradiation. Glutamine (Gln) and glucose (Glc) are important nutrients for tumor cells, playing important roles as nitrogen and carbon sources to meet the bioenergetic, biosynthetic and reductive needs. Defective blood supply in solid tumors may result in nutrient insufficiency, including Gln and Glc insufficiency. It remains unknown how tumor cells respond to Gln- and Glc- insufficient microenvironment and regulate their viability and proliferation. Using gene profiling analysis with microarrays, we have identified STC2 as one of the most up-regulated genes in response to either Gln- or Glc- deprivation. We confirm that Gln-deprivation stimulates STC2 expression at both mRNA and protein levels in various human tumor cells by quantitative reverse transcription-real-time PCR and Western blot, respectively. Furthermore, we find that Gln-insufficiency activates both nuclear factor-κB (NF-κB) and ATF4 signaling pathways, which synergistically up-regulates STC2. Finally, we demonstrate that up-regulation of STC2 attenuates tumor cell proliferation but reduces apoptosis in Gln-insufficient conditions. These findings suggest a novel model that STC2 reprograms the priority of tumor cells from rapid proliferation to survival under stress conditions, indicating that STC2 may be a novel target for cancer therapy.
Citation Format: Shuo Qie, Lifeng Tian, Chenguang Wang, Nianli Sang. Stanniocalcin 2 attenuates tumor cell proliferation but suppresses apoptosis in nutrient-deprived conditions. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-135. doi:10.1158/1538-7445.AM2013-LB-135