Abstract 1601: Human colorectal cancer marker PC(16:0/16:1) induces cell growth by activating Akt and Erk pathways
Authors: Kurabe Nobuya , Nakamura Toshio , Kurachi Kiyotaka , Kahyo Tomoaki , Shinmura Kazuya , Setou Mitsutoshi , Sugimura Haruhiko 
Published: May 2015

The identification of cancer biomarkers is critical for target-linked cancer therapy. Numerous protein, glycoprotein, and nucleic acids markers are known, but there has been a limitation to pickup a lipid marker in tumor tissues due to difficulty in surveillance of lipid molecules in tissues. The overall level of phosphatidylcholine (PC) is elevated in colorectal cancer (CRC), buy the exact nature of PC change in CRC remains to be elucidated. In our previous literature, to investigate which species of PC is overexpressed in colorectal cancer, an imaging mass spectrometry (MS) was performed using a panel of non-neoplastic mucosal and CRC tissues. We had performed principal component analysis (PCA) of the mass spectrum data and successfully differentiate CRC to adjacent non-neoplastic colorectal mucosal cells. Using PCA, a novel biomarker, phosphatidylcholine (PC)(16:0/16:1), had been also identified in CRC. Specifically, elevated levels of PC(16:0/16:1) expression had been observed in a more advanced stage of CRC. Our data further showed that PC(16:0/16:1) was specifically localized in the cancer region when examined using imaging mass spectrometry. Notably, because the ratio of PC(16:0/16:1) to lyso-PC(16:0) had been higher in CRC, we had postulated that lyso-PC acyltransferase (LPCAT) activity is elevated in CRC. In an in vitro analysis, we had shown that LPCAT4 is involved in the deregulation of PC(16:0/16:1) in CRC. That study had indicated the potential usefulness of PC(16:0/16:1) for the clinical diagnosis of CRC and implicate LPCAT4 in the elevated expression of PC(16:0/16:1) in CRC. To investigate usefullness and the molecular mechanism regarding the PC(16:0/16:1) upregulation in CRC, we next focused on the responses of cells when PC(16:0/16:1) was administrated in vitro.

To further analyze the effects of PC(16:0/16:1) on the growth of several culture cells, we added PC(16:0/16:1) to the culture media of HCT116 colorectal cancer cell line and NIH3T3 non-cancerous cell line. For the analysis of the signaling pathway of the cells, western blotting were carried out using various phosphorylation specific antibodies when NIH3T3 cells were subjected to PC(16:0/16:1). We also tried to specify the target genes affected by the addition of PC(16:0/16:1) into the NIH3T3 cell.

PC(16:0/16:1) induced the increase in the growth rate of NIH3T3 cell line but not HCT116 cell line by about two fold. Phosphorylations of Akt and Erk were increased by the administration of PC(16:0/16:1) by about 1.5 and 3 fold, respectively. We expected some genes may be listed as PC(16:0/16:1) target ones by microarray analysis. The result using 3D-gene chip microarray will be presented.

PC(16:0/16:1) induce cell growth by activating Akt and Erk pathway. Possible PC(16:0/16:1) target genes will be shown.

Citation Format: Nobuya Kurabe, Toshio Nakamura, Kiyotaka Kurachi, Tomoaki Kahyo, Kazuya Shinmura, Mitsutoshi Setou, Haruhiko Sugimura. Human colorectal cancer marker PC(16:0/16:1) induces cell growth by activating Akt and Erk pathways. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1601. doi:10.1158/1538-7445.AM2014-1601