Identification of DEC1-interacting protein DNAJB6 and its role in esophageal squamous cell carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) has an especially high incidence in China, with five-year survival rates in Hong Kong being of ∼14%. Previously, a critical region at 9q33-34 was narrowed down and identified to be associated with tumor-suppressive function in ESCC. Within this region, Deleted in Esophageal Cancer 1 (DEC1), was identified to suppress anchorage-independent growth and tumorigenesis. In this study, we searched for DEC1-interacting partners by yeast two-hybrid screening. DNAJ (Hsp40) homologue subfamily B member 6 (DNAJB6) was identified as a DEC1-interacting protein and its interaction was further confirmed by the GST pull-down assay and co-localization studies. A putative DEC1-interacting sequence was mapped to the C-terminal end of DNAJB6 coding sequence. Using a tissue microarray constructed with tissues from Hong Kong, significantly higher survival in distant metastasis-free (M0) patients was found to be associated with higher DNAJB6 nuclear staining. DNAJB6 is down-regulated in 12 out of 14 (85.7%) ESCC cell lines, when compared to expression in an immortalized normal esophageal epithelial cell line. The two isoforms of DNAJB6 have distinct cellular localizations. DNAJB6a is mainly localized to the nucleus, while DNAJB6b shows diffuse staining in both the nucleus and cytoplasm. Through migration/invasion assay, we showed that expressions of both isoforms were inversely associated with migration/invasion ability of ESCC cell lines. These results suggest DNAJB6 plays a role in ESCC migration/invasion and metastasis. This gene may play a critical role in ESCC metastasis in an isoform-specific manner, which will be the focus of future studies.