Identification of a novel p53 target, COL17A1, that inhibits breast cancer cell migration and invasion

Abstract

p53 mutation is a marker of poor prognosis in breast cancers. To identify downstream targets of p53, we screened two transcriptome datasets, including cDNA microarrays of MCF10A breast epithelial cells with wild-type p53 or p53-null background, and RNA sequence analysis of breast invasive carcinoma. Here, we unveil ten novel p53 target candidates that are up-regulated after the induction of p53 in wild-type cells. Their expressions are also high in breast invasive carcinoma tissues with wild-type p53. The GO analysis identified epidermis development and ectoderm development, which COL17A1 participates, as significantly up-regulated by wild-type p53. The COL17A1 expressions increased in a p53-dependent manner in human breast cells and mouse mammary tissues. Reporter assay and ChIP assay identified intronic p53-binding sequences in the COL17A1 gene. The MDA-MB-231 cells that genetically over-express COL17A1 gene product exhibited reduced migration and invasion in vitro. Similarly, COL17A1 expression was decreased in metastatic tumors compared to primary tumors and normal tissues, even from the same patients. Moreover, high COL17A1 expression was associated with longer survival of patients with invasive breast carcinoma. In conclusion, we revealed that COL17A1 is a novel p53 transcriptional target in breast tissues that inhibits cell migration and invasion and is associated with better prognosis.

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“…In line with this view, the TCGA-BRCA data showed that COL17A1 mRNA levels were significantly lower in metastasized breast cancer cells than in corresponding primary breast cancer cells. Taken together, the findings reported by Yodsurang et al [3] provide new insight into the p53-mediated tumor suppression system and a step forward to complete the p53 puzzle.…”

“…In the current issue of Oncotarget, Matsuda and colleagues systematically analyzed the p53 targetome in two different studies [3,4]. In the first study, they screened p53-induced genes using microarray data from Adriamycin (ADR)-treated MCF10A breast epithelial cells and RNA sequencing (RNA-seq) data from Breast Invasive Carcinoma (BRCA) in The Cancer Genome Atlas (TCGA) [5].…”

Synergistic activation of p53 by actinomycin D and nutlin-3a is associated with the upregulation of crucial regulators and effectors of innate immunity

“…Here, wanted to show an example of increased secretion of an extracellular protein induced by treatment with A + N. We selected COL17A1 protein. Its gene is directly regulated by p53 [39]. We took advantage of the fact that COL17A1 is unusual collagen molecule with its full-length form anchored in cellular membrane (~180 kDa molecule) and its extracellular domain (~120 kDa ectodomain) shed to cell environment.…”

Identification of core genes and pathways in melanoma metastasis via bioinformatics analysis

“…COL17A1 encodes the protein collagen alpha-1(XVII) chain that is responsible for adhesion of cell and matrix. Matsuda K. et al showed COL17A1 was modulated by p53, and it inhibited breast cancer cell migration and invasion [41]. Furthermore, Pascal H. G. Duijf and his colleagues reported that COL17A1 was overexpressed in cervical and other epithelial cancers and predicted an increased metastatic signature [42].…”