Heat shock protein 47 promotes cell migration and invasion through AKT signal in non-small cell lung cancer

Abstract

Lung cancer is one of the most lethal malignancies, with the highest number of cases and deaths. Non-small cell lung cancer (NSCLC) is the most ordinary type of pathology in lung cancer. Meanwhile, various researchers have reported that heat shock protein 47 (HSP47) plays a vital regulatory role in cancer. However, the role of HSP47 in NSCLC is not clear. Consequently, the current study set out to investigate the role of HSP47 in the pathogenesis of NSCLC. First, we evaluated the expression patterns of HSP47 in NSCLC cell lines related to human normal lung epithelial cells, and HSP47 was found to be highly expressed in NSCLC cell lines. In addition, inhibiting the expression of HSP47 brought about marked repression in cell proliferation, migration and invasion in PC-9 cells. On the contrary, cell proliferation, migration and invasion were all elevated after over-expression of HSP47. Mechanistical experimentation further illustrated that protein kinase B (AKT) signal was repressed after inhibition of HSP47, and the influence of sh-HSP47 on cell proliferation, migration and invasion was countered by epidermal growth factor. Lastly, in-vivo animal models demonstrated that inhibition of HSP47 repressed cell tumorigenesis and AKT signal. Collectively, our findings illustrated that HSP47 was highly expressed in NSCLC cell lines, whereas inhibition of HSP47 repressed cell migration and invasion by diminishing the AKT signal. Inhibition of HSP47 also exhibited strong therapeutic effects on NSCLC in vivo

Overexpression of heat‐shock protein 47 impacts survival of patients with oral squamous cell carcinoma

“…22 Loss-of-function studies based on shRNA against HSP47 revealed that HSP47 contributes to proliferation, migration, and invasion of lung cancer cells. 10 In gastric cancer, HSP47-silenced cells demonstrated reduction in WNT/β-catenin signaling pathway proteins, including Snail1, Slug, and TWIST, which control epithelial-mesenchymal transition, culminating in decreased cell migration and invasion. 9 Our data did not demonstrate that HSP47 knockdown alters OSCC cell survival or sensitize cells to cisplatin, in spite of HSP47 levels has been correlated to tumor progression and response to chemotherapy in glioblastomas, 27 and overexpression of HSP47 conferred chemoresistance to 5-fluorouracil in colorectal cancer 5 and to gemcitabine, a nucleotide analog included in the multidrug chemotherapy regimen in many tumor types, in pancreatic cancer.…”

“…The knockdown of HSP47, which was expressed in high levels in TE‐8 cells, an esophageal cancer cell line, significantly inhibited proliferation and colony formation, conferring an oncogenic potential on esophageal squamous cell carcinoma 22 . Loss‐of‐function studies based on shRNA against HSP47 revealed that HSP47 contributes to proliferation, migration, and invasion of lung cancer cells 10 . In gastric cancer, HSP47‐silenced cells demonstrated reduction in WNT/β‐catenin signaling pathway proteins, including Snail1, Slug, and TWIST, which control epithelial–mesenchymal transition, culminating in decreased cell migration and invasion 9 .…”

“…7 In the neoplastic context, the effects of HSP47, depending of the cell type, were related to activation of pathways involving transforming growth factor-beta (TGF-β), 8 Wnt/β-catenin, 9 and Akt. 10 The expression and the prognostic significance of HSP47 in head and neck squamous cell carcinomas have been revealed in some studies 7,[11][12][13] ; however, little is known about its biological role in oral squamous cell carcinoma (OSCC), the most common malignancy in the oral cavity, which displays high prevalence and mortality worldwide. Lee et al 14 demonstrated that HSP47 levels are significantly higher in areca quid chewing-associated OSCCs compared to normal oral tissues, and in a recent study, Fu et al 15 demonstrated that HSP47 was one of the 18 upregulated genes in OSCC compared to normal tissue after combining two GEO microarray datasets.…”

“…Aside from its canonical function as molecular chaperone for nascent chains of collagen, the studies are revealing that HSP47 influences numerous cellular processes including proliferation, apoptosis, and invasion, 4 and HSP47 expression is correlated with chemoresistance 5,6 and poor prognosis in solid tumors 7 . In the neoplastic context, the effects of HSP47, depending of the cell type, were related to activation of pathways involving transforming growth factor‐beta (TGF‐β), 8 Wnt/β‐catenin, 9 and Akt 10 …”

HSP47: A Therapeutic Target in Pulmonary Fibrosis

“…The aberrant expression of the SERPINH1 gene has been shown to be closely linked to tumor growth, invasion, and metastasis in cervical squamous cell carcinoma and gastric cancer [ 65 , 66 ]. In non-small cell lung cancer cell lines, HSP47 was highly expressed, whereas the inhibition of HSP47 repressed cell migration and invasion by diminishing the AKT signal [ 67 ].…”