PSF1, a DNA replication factor expressed widely in stem and progenitor cells, drives tumorigenic and metastatic properties

Yumi Nagahama, Masaya Ueno, Satoru Miyamoto, Eiichi Morii, Takashi Minami, Naoki Mochizuki, Hideyuki Saya, Nobuyuki Takakura

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

PSF1 (partner of sld five 1) is an evolutionarily conserved DNA replication factor implicated in DNA replication in lower species that is strongly expressed in a wide range of normal stem cell populations and progenitor cell populations. Because stem and progenitor cells possess high proliferative capacity, we hypothesized that PSF1 may play an important role in tumor growth. To begin to investigate PSF1 function in cancer cells, we cloned the mouse PSF1 promoter and generated lung and colon carcinoma cells that stably express a PSF1 promoter-reporter gene. Reporter expression in cells correlated with endogenous PSF1 mRNA expression. In a tumor cell xenograft model, high levels of reporter expression correlated with high proliferative activity, serial transplantation potential, and metastatic capability. Notably, cancer cells expressing reporter levels localized to perivascular regions in tumors and displayed expression signatures related to embryonic stem cells. RNAi-mediated silencing of endogenous PSF1 inhibited cancer cell growth by disrupting DNA synthesis and chromosomal segregation. These findings implicate PSF1 in tumorigenesis and offer initial evidence of its potential as a theranostic target.

Original languageEnglish
Pages (from-to)1215-1224
Number of pages10
JournalCancer Research
Volume70
Issue number3
DOIs
Publication statusPublished - 2010 Feb 1

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DNA Replication
Stem Cells
Neoplasms
Embryonic Stem Cells
Growth
RNA Interference
Reporter Genes
Heterografts
Population
Colon
Carcinogenesis
Reference Values
Transplantation
Carcinoma
Lung
Messenger RNA
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nagahama, Y., Ueno, M., Miyamoto, S., Morii, E., Minami, T., Mochizuki, N., ... Takakura, N. (2010). PSF1, a DNA replication factor expressed widely in stem and progenitor cells, drives tumorigenic and metastatic properties. Cancer Research, 70(3), 1215-1224. https://doi.org/10.1158/0008-5472.CAN-09-3662

PSF1, a DNA replication factor expressed widely in stem and progenitor cells, drives tumorigenic and metastatic properties. / Nagahama, Yumi; Ueno, Masaya; Miyamoto, Satoru; Morii, Eiichi; Minami, Takashi; Mochizuki, Naoki; Saya, Hideyuki; Takakura, Nobuyuki.

In: Cancer Research, Vol. 70, No. 3, 01.02.2010, p. 1215-1224.

Research output: Contribution to journalArticle

Nagahama, Yumi ; Ueno, Masaya ; Miyamoto, Satoru ; Morii, Eiichi ; Minami, Takashi ; Mochizuki, Naoki ; Saya, Hideyuki ; Takakura, Nobuyuki. / PSF1, a DNA replication factor expressed widely in stem and progenitor cells, drives tumorigenic and metastatic properties. In: Cancer Research. 2010 ; Vol. 70, No. 3. pp. 1215-1224.
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