ROR1 sustains RTK-mediated survival signaling in lung adenocarcinoma

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461187
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Nagoya University
• Principal Investigator: YAMAGUCHI TOMOYA 名古屋大学, 医学(系)研究科(研究院), 特任助教 (70452191)
• Co-Investigator(Renkei-kenkyūsha): YANAGISAWA Kiyoshi 名古屋大学, 大学院医学系研究科, 講師 (20372112)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 肺腺がん / ROR1 / カベオラ / EGFR-TKI / 薬剤耐性

Outline of Final Research Achievements

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) sustains prosurvival signaling directly downstream of the lineage-survival oncogene NKX2-1/TTF-1 in lung adenocarcinoma. We analyzed the effects of siROR1 treatment on the phosphorylation state using a human phospho-RTK array, which revealed a significant decrease in the phosphorylation of multiple RTKs in both NCI-H1975 and PC-9 lung adenocarcinoma cells. We found that ROR1 knockdown effectively overcame ligand-mediated EGFR-TKI resistance in PC-9 or NCI-H1975 cell. These results suggest that ROR1 repression inhibits lung adenocarcinoma cells with acquired EGFR-TKI resistance through bypass pathways. Finally, we also found that ROR1 knockdown significantly decreased the protein expression of CAV1, the essential structural component of caveolae, in lung adenocarcinoma cells.

Free Research Field

分子腫瘍学