PFDN1, an indicator for colorectal cancer prognosis, enhances tumor cell proliferation and motility through cytoskeletal reorganization.

Abstract

Prefoldin (PFDN) subunits have been reported upregulated in various tumor types, while the expression and functions of PFDN1 (PFDN subunit 1) in colorectal cancer (CRC) are not well elucidated. The aim of this study was to investigate the use of PFDN1 as a poor prognosis indicator for CRC and explore the functions of PFDN1 in CRC. The relationship between PFDN1 expression and CRC clinical-pathological statistics was detected on the tissue microarray containing 145 cases of CRC. ShRNA was used to silence PFDN1 expression in SW480 and RKO CRC cells, and these transfected cells were analyzed for changes in proliferation, colony formation, cell cycle, migration, and invasion. Immunofluorescence and immunoblot were used to determine the remodeling of the F-actin and α-tubulin. Finally, tumor growth on nude mice was observed and measured. In this study, we found PFDN1 was upregulated in CRC tissues compared with adjacent normal tissues. Also, PFDN1 expression positively correlated with tumor size and tumor invasion. Moreover, after silencing PFDN1 in SW480 and RKO cells, the proliferation and motility of CRC cells were significantly suppressed. The inhibitory effect of PFDN1 on tumor cell growth and motility was partially due to G2/M cell cycle blockage and cytoskeletal deficiency. Finally, in vivo assay showed that downregulation of PFDN1 inhibited tumor growth on nude mice and PFDN1 expression correlated with higher levels of Ki-67 staining. These findings indicate that PFDN1 was involved in the progression of CRC, and provide new insights into PFDN1 as a potential therapeutic target for CRC treatment.

• Authors: Puxiongzhi Wang, Jingkun Zhao, Xiao Yang, Shaopei Guan, Hao Feng, Dingpei Han, Jun Lu, Baochi Ou, Runsen Jin, Jing Sun, Yaping Zong, Bo Feng, Junjun Ma, Aiguo Lu, Minhua Zheng
• Journal: Medical oncology (Northwood, London, England) (Med Oncol) Vol. 32 Issue 12 Pg. 264 (Dec 2015) ISSN: 1559-131X [Electronic] United States
• PMID: 26553318 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Molecular Chaperones
• prefoldin

Topics

• Aged
• Animals
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Cohort Studies
• Colorectal Neoplasms (metabolism, mortality)
• Cytoskeleton (metabolism)
• Down-Regulation
• Female
• Gene Silencing
• Humans
• Male
• Mice
• Mice, Nude
• Middle Aged
• Molecular Chaperones (genetics, metabolism)
• Prognosis