title: PTRF suppresses the progression of colorectal cancers.
abstract: As a key component of caveolae structure on the plasma membrane, accumulated evidence has suggested that Polymerase I and Transcript Release Factor (PTRF) plays a pivotal role in suppressing the progression of human malignances. However, the function of PTRF in the development of colorectal cancers is still unclear. Here we report that the expression of PTRF is significantly reduced in tumor tissues derived from human patients with colorectal cancers, and that the downregulation of PTRF correlates to the advanced stage of the disease. In addition, we found that the expression of PTRF negatively regulates the tumorigenic activities of colorectal cell lines (Colo320, HT29 and CaCo2). Furthermore, ectopic PTRF expression caused significant suppression of cellular proliferation, and anchorage-independent colony growth of Colo320 cells, which have the lowest expression level of PTRF in the three studied cell lines. Meanwhile, shRNA mediated knockdown of PTRF in CaCo2 cells significantly promoted cellular proliferation and anchorage-independent colony growth. In addition, in vivo assays further revealed that tumor growth was significantly inhibited in xenografts with ectopic PTRF expression as compared to untreated Colo320 cells, but was markedly enhanced in PTRF knockdown CaCo2 cells. Biochemical studies revealed that overexpression of PTRF led to the suppression of the AKT/mTOR pathway, as evidenced by reduced phosphorylation of AKT, mTOR, and downstream MMP-9. Thus, these findings, for the first time, demonstrated that PTRF inhibits the tumorigenesis of colorectal cancers and that it might serve as a potential therapeutic target for human colon cancer patients.
authors.affiliation: Gastroenterology Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Yongqiu
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Physical Education and Human Performance, Central Connecticut State University, New Britain, CT, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Orange
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Yang
authors.affiliation: Gastroenterology Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Gastroenterology Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Tan
authors.affiliation: Gastroenterology Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Xiangxue
authors.initials: X
authors.lastname: Ma
authors.affiliation: Gastroenterology Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Tin
authors.initials: T
authors.lastname: Chen
authors.affiliation: Gastroenterology Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Yin
authors.affiliation: Gastroenterology Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D047368:Tumor Burden
chemical_list: C497835:CAVIN1 protein, human; D016601:RNA-Binding Proteins; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: PTRF; colorectal cancer; mTOR; progression