The Role of Heat Shock Protein 40 in Carcinogenesis and Biology of Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide. Despite the enormous amount of effort in the diagnosis and treatment of CRC, the overall survival rate of patients remains low. The precise molecular and cellular basis underlying CRC has not been completely understood yet. Over time, new genes and molecular pathways involved in the pathogenesis of the disease are being identified. The accurate discovery of these genes and signaling pathways are important and urgent missions for the next generation of anticancer therapy research. Chaperone DnaJ, also known as Hsp40 (heat shock protein 40), has been of particular interest in CRC pathogenesis, as it is involved in the fundamental cell activities for maintaining cellular homeostasis. Evidence shows that protein family members of DnaJ/Hsp40 play both roles, enhancing and reducing the growth of CRC cells. In the present review, we focus on the current knowledge of the molecular mechanisms responsible for DnaJ/Hsp40 in CRC carcinogenesis and biology.

Keywords: Heat shock protein 40; carcinogenesis; chaperone DnaJ; colorectal cancer; metastasis; treatment.

Fig. (1)

Role of Hsp40 in cancer development.

Fig. (2)

Overexpression of Hsp40 family members in colon and rectum adenocarcinomas (COAD and READ, respectively). In each box plot, gene expression levels are compared between cancer and normal samples. The plots were generated by OncoDB (http://oncodb.org).

Fig. (3)

The effect of expression levels of Hsp40 family members on overall survival and disease-free survival. Colon and rectum adenocarcinoma patients were included. TPM and HR represent transcript per million reads and hazard ratio, respectively. The plots were generated by GEPIA (© 2017 Zefang Tang, Chenwei Li, Boxi Kang. Zhang's Lab).

Fig. (4)

The interaction and regulation of the Hsp70 machinery cycle by Hsp40. I: The delivery of nascent or misfolded substrates to ATP-bound Hsp70; II: Hydrolysis of ATP to ADP; III & IV: NEF (Nucleotide exchange factor) binds to Hsp70, catalyzing the exchange of ADP for ATP; V: ATP binds to the Hsp70’s ATPase domain.