Abstract 1641: Complex behavior of ALDH1A1 and IGFBP1 in liver metastasis of colorectal cancer

Abstract

Abstract The present study aimed to identify upregulated genes associated with colorectal cancer (CRC) liver metastasis (CLM) using our dataset (GSE50760) previously established by RNA sequencing and to verify their biological behavior. Candidate genes were assessed for their role in tumor proliferation, invasion, and the expression of epithelial-mesenchymal transition/CRC stem cell (EMT/CSC)-related molecules. The role of the identified genes in CLM was verified in mice after intrasplenic transplantation of CRC cells. Of nine candidate genes, ALDH1A1 and IGFBP1 were selected and showed few post-translational changes. The upregulation of ALDH1A1 and IGFBP1 significantly and time-dependently decreased cell proliferation (p ≤ 0.001-0.003) and suppressed invasiveness by ≥3 fold over control cells (p < 0.001) in the SW480 cell line, whereas it had a mild effect on reducing SW620 cell proliferation. EMT/CSC-related molecules showed different patterns of expression in CLM tissues and treated CRC cells. The cadherin switch, namely, N-cadherin upregulation with E-cadherin downregulation, was not observed in CLM tissues and treated CRC cells. Persistent overexpression of β-catenin, vimentin, and ZO-1 in IGFBP1-overexpressing SW480 cells may have contributed to CLM development in mice implanted with IGFBP1-overexpressing cells (CLM occurrences: SW480/IGFBP1 transfected mice vs. SW480/vector and /ALDH1A1 transfected mice, 4/8 vs. 0/10, p = 0.023). ALDH1A1 and IGFBP1 were differentially overexpressed in CLM and may play a dual role, functioning as tumor suppressors and metastasis promoting genes in CRC. Unidentified behaviors of these genes may facilitate the reassessment of their potential value as CLM modulators and as therapeutic targets. Citation Format: Jin Cheon Kim, Ye Jin Ha, Ka Hee Tak, Seon Ae Roh, Chan Wook Kim, Tae Won Kim, Dong-Hyung Cho, Seon-Kyu Kim, Seon-Young Kim, Yong Sung Kim. Complex behavior of ALDH1A1 and IGFBP1 in liver metastasis of colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1641.