Open AccessIdentification and characterization of a metastatic suppressor BRMS 1L as a target gene of p53
Author(s) -
Koyama Ryota,
Tamura Miyuki,
Nakagaki Takafumi,
Ohashi Tomoko,
Idogawa Masashi,
Suzuki Hiromu,
Tokino Takashi,
Sasaki Yasushi
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13420
Subject(s) - ectopic expression , biology , cancer research , gene knockdown , cancer , metastasis , cancer cell , tumor suppressor gene , suppressor , cell cycle , microarray analysis techniques , cell , gene , carcinogenesis , gene expression , genetics
The tumor suppressor p53 and its family members, p63 and p73, play a pivotal role in the cell fate determination in response to diverse upstream signals. As transcription factors, p53 family proteins regulate a number of genes that are involved in cell cycle arrest, apoptosis, senescence, and maintenance of genomic stability. Recent studies revealed that p53 family proteins are important for the regulation of cell invasion and migration. Microarray analysis showed that breast cancer metastasis suppressor 1‐like ( BRMS 1L ) is upregulated by p53 family proteins, specifically p53, TA p63γ, and TA p73β. We identified two responsive elements of p53 family proteins in the first intron and upstream of BRMS 1L . These response elements are well conserved among mammals. Functional analysis showed that ectopic expression of BRMS 1L inhibited cancer cell invasion and migration; knockdown of BRMS 1L by si RNA induced the opposite effect. Importantly, clinical databases revealed that reduced BRMS 1L expression correlated with poor prognosis in patients with breast and brain cancer. Together, these results strongly indicate that BRMS 1L is one of the mediators downstream of the p53 pathway, and that it inhibits cancer cell invasion and migration, which are essential steps in cancer metastasis. Collectively, our results indicate that BRMS 1L is involved in cancer cell invasion and migration, and could be a therapeutic target for cancer.