HspB5 correlates with poor prognosis in colorectal cancer and prompts epithelial-mesenchymal transition through ERK signaling.

Qinghua Li,Ping Xu,Yuexing Lai,Yanlan Wang,Zhiwen Yang,Aamir Ahmad

doi:10.1371/journal.pone.0182588

Abstract

Alpha B-crystallin (HspB5) is abnormally expressed in tumor tissues and portends a poor prognosis in cancer patients. However, the role of HspB5 in colorectal cancer (CRC) is still unclear. Seventy CRC patients and 40 healthy volunteers were sampled from August 2012 to March 2015 in order to determine the clinical significance of HspB5. In vitro cellular studies were used to validate its molecular mechanisms in CRC. Our clinical data indicated that HspB5 was up-regulated, and had a positive association with TNM stage CRC patients. The expression level of HspB5 in CRC patients was closely correlated with MMP7 and E-cadherin, two core epithelial–mesenchymal transition (EMT) gene products. The in vitro studies revealed that high HspB5 expression could prompt tumor cell proliferation and invasion, as well as EMT. Gene-microarray analysis suggested three significant signaling pathways (PI3K, p38 and ERK) were involved in HspB5-induced EMT. Signal transduction pathway inhibitors and HspB5 gene knockdown models suggested that HspB5 promotes CRC tumorigenesis and EMT progression through ERK signaling pathways. In summary, HspB5 maybe trigger the EMT in CRC by activating the ERK signaling pathway. It is a potential tumor biomarker for CRC diagnosis and prognosis.

Highlights

Colorectal cancer (CRC) is the third most prevalent cancer in China and accounts for the major cause of cancer-related deaths[1]
There was a significant difference in gene expression among CRC patients
This study clearly indicates that HspB5 is a candidate tumor suppressor which was markedly up-regulated in CRC, and potently induces the epithelial–mesenchymal transition (EMT) process by activating the extracellular regulated protein kinases (ERK) signaling pathway

Summary

Introduction

Colorectal cancer (CRC) is the third most prevalent cancer in China and accounts for the major cause of cancer-related deaths[1]. The occurrence and progression of CRC maybe a multi-step, complex process associated with multiple oncogenes and tumor suppressors[2]. Great efforts have been made to better understand the molecular mechanism relevant to CRC and to improve its therapy, these aspects of CRC are still largely unknown. The underlying pathogenesis associated with CRC requires further study for the development of novel diagnostic and therapeutic approaches. Alpha B-crystallin (HspB5) is a cytoprotective molecular chaperone and small heat-shock protein[3].

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Results

Conclusion