Abstract 2358: Molecular chaperones as a common set of proteins that regulate the invasion phenotype of head and neck cancer

Abstract

Abstract Purpose: The goal of this study was to establish a common set of molecules that regulate cell invasion in head and neck cancer (HNC). Experimental design: Five invasive sublines derived from HNC cell lines were established using the Matrigel selection method. Proteomic technology, MetaCore™ algorithm, and RT-PCR methods were used to search for molecules that contribute to the invasion phenotype. Cellular functional analyses and clinical association studies were applied to examine the significance of the molecules. Results: Fifty-two proteins were identified in more than two of the four independent proteomic experiments, including 10 (19%) molecular chaperones. Seven chaperones were confirmed to be differentially expressed in five sublines: Hsp90α, Hsp90β, Hsp90-B1/Gp96, Hsp70-A5/Grp78, HYOU1 up-regulation, while Hsp60 and GANAB down-regulation. Four molecules with the highest differential expressions (> 4-fold) were further investigated. In all cell lines, knockdown of Hsp60 or GANAB and silencing of Gp96 or Grp78 considerably enhanced or reduced cell migration and invasion, respectively. Clinical association studies consistently revealed that low levels of Hsp60 or GANAB and high levels of Gp96 or Grp78 are significantly associated with advanced cancer (P<0.001 to P = 0.047, respectively, for the four molecules) and poor survival (P<0.001 to P=0.025, respectively, for the four molecules). Conclusion: In conclusion, our study defined molecular chaperones as a common set of proteins that regulate the invasion phenotype of head and neck cancer. Loss of the tumor suppression function of Hsp60 or GANAB and acquisition of the oncogenic function of Gp96 or Grp78 contribute to aggressive cancers. These molecules may serve as prognostic markers and targets for cancer drug development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2358. doi:10.1158/1538-7445.AM2011-2358