Research Papers:

Identification and characterization of the intercellular adhesion molecule-2 gene as a novel p53 target

Yasushi Sasaki, Miyuki Tamura, Kousuke Takeda, Kazuhiro Ogi, Takafumi Nakagaki, Ryota Koyama, Masashi Idogawa, Hiroyoshi Hiratsuka, Takashi Tokino _

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Oncotarget. 2016; 7:61426-61437. https://doi.org/10.18632/oncotarget.11366

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Yasushi Sasaki1,*, Miyuki Tamura1,*, Kousuke Takeda1,2,*, Kazuhiro Ogi2, Takafumi Nakagaki1,2, Ryota Koyama1, Masashi Idogawa1, Hiroyoshi Hiratsuka2, Takashi Tokino1

1Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan

2Department of Oral Surgery, Sapporo Medical University, Sapporo, Japan

*These authors contributed equally to this work

Correspondence to:

Takashi Tokino, email: tokino@sapmed.ac.jp

Yasushi Sasaki, email: yasushi@sapmed.ac.jp

Keywords: ICAM2, p53, p53 family, cell invasion, cell migration

Received: January 29, 2016     Accepted: August 08, 2016     Published: August 18, 2016


The p53 tumor suppressor inhibits cell growth through the activation of both cell cycle arrest and apoptosis, which maintain genome stability and prevent cancer development. Here, we report that intercellular adhesion molecule-2 (ICAM2) is transcriptionally activated by p53. Specifically, ICAM2 is induced by the p53 family and DNA damage in a p53-dependent manner. We identified a p53 binding sequence located within the ICAM2 gene that is responsive to wild-type p53, TAp73, and TAp63. In terms of function, we found that the ectopic expression of ICAM2 inhibited cancer cell migration and invasion. In addition, we demonstrated that silencing endogenous ICAM2 in cancer cells caused a marked increase in extracellular signal-regulated kinase (ERK) phosphorylation levels, suggesting that ICAM2 inhibits migration and invasion of cancer cells by suppressing ERK signaling. Moreover, ICAM2 is underexpressed in human cancer tissues containing mutant p53 as compared to those with wild-type p53. Notably, the decreased expression of ICAM2 is associated with poor survival in patients with various cancers. Our findings demonstrate that ICAM2 induction by p53 has a key role in inhibiting migration and invasion.

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