Abstract
Chromobox protein homolog 7 (CBX7), one of the polycomb group (PcG) proteins, is a transcriptional repressor involved in the regulation of cell proliferation and senescence. In the present study, we showed that CBX7 negatively regulates the proliferation, viability, chemoresistance, and migration of pancreatic cancer cells. Overexpression of CBX7 significantly inhibited the proliferation of pancreatic cancer cells in vitro and in vivo. Depletion of CBX7 facilitated their growth. CBX7 also impaired the viability and chemoresistance of pancreatic cancer cells. Transwell assays showed that CBX7 reduces the migratory capacity of pancreatic cancer cells. Of note, CBX7 reduced PTEN/Akt signaling in pancreatic cancer cells by increasing PTEN transcription, suggesting involvement of PTEN/Akt pathway in the tumor suppressive activity of CBX7. In addition, immunohistochemical analysis the CBX7 and PTEN expression in 74 surgically resected pancreatic ductal adenocarcinoma (PDAC) specimens revealed that CBX7 expression is significantly downregulated in pancreatic ductal adenocarcinoma, compared to normal pancreatic tissues. Reduced expression of CBX7 and PTEN was associated with increased malignancy grade in pancreatic adenocarcinoma, whereas maintenance of CBX7 and PTEN expression showed a trend toward a longer survival. These findings suggest CBX7 is an important tumor suppressor that negatively modulates PTEN/Akt signaling during pancreatic tumorigenesis.
Highlights
90% of all pancreatic cancer cases are fatal, making it one of the most lethal malignancies and a major worldwide health burden [1, 2]
Reduced expression of Chromobox protein homolog 7 (CBX7) and PTEN was associated with increased malignancy grade in pancreatic adenocarcinoma, whereas maintenance of CBX7 and PTEN expression showed a trend toward a longer survival
Western blotting results revealed that the cellular level of CBX7 was markedly upregulated following CBX7-lentivirus infection in both Panc-1 and MIA PaCa-2 pancreatic cancer cells (Figure 1A and 1B)
Summary
90% of all pancreatic cancer cases are fatal, making it one of the most lethal malignancies and a major worldwide health burden [1, 2]. A positive correlation between loss of CBX7 expression and poor prognosis was found in human colon and breast carcinomas [12, 13]. These results indicate that the precise role of CBX7 in cancer development may vary between different cancer types. Despite the fact that loss of CBX7 expression has been associated with enhanced malignancy in pancreatic cancer, the underlying molecular mechanism remains to be elucidated [14]. We investigate the effect of CBX7 on pancreatic cancer development and explore the underlying molecular mechanisms
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