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RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE212399 | GEO | 2022/10/26

REPOSITORIES: GEO

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RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer.

Project description:CD271 (also referred to as nerve growth factor receptor or p75NTR) is expressed on cancer stem cells in hypopharyngeal cancer (HPC) and regulates cell proliferation. Because elevated expression of CD271 increases cancer malignancy and correlates with poor prognosis, CD271 could be a promising therapeutic target; however, little is known about the induction of CD271 expression and especially its promoter activity. In this study, we screened transcription factors and found that RELA (p65), a subunit of nuclear factor kappaB (NF-κB), is critical for CD271 transcription in cancer cells. Specifically, we found that RELA promoted CD271 transcription in squamous cell carcinoma cell lines but not in normal epithelium and neuroblastoma cell lines. Within the CD271 promoter sequence, region + 957 to + 1138 was important for RELA binding, and cells harboring deletions in proximity to the + 1045 region decreased CD271 expression and sphere-formation activity. Additionally, we found that clinical tissue samples showing elevated CD271 expression were enriched in RELA-binding sites and that HPC tissues showed elevated levels of both CD271 and phosphorylated RELA. These data suggested that RELA increases CD271 expression and that inhibition of RELA binding to the CD271 promoter could be an effective therapeutic target.

| S-EPMC9588052 | biostudies-literature

RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer [dataset 2]

Project description:To investigate the RELA-induced CD271 signaling, RELA-binding sequence of CD271 promoter region was deleted and performed microarray analysis

2022-10-26 | GSE212398 | GEO

RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer [dataset 1]

Project description:To investigate the mechanisms of CD271 transcription, we analyzed the difference between sorted CD271-low and CD271 expression-recovered cells.

2022-10-26 | GSE212397 | GEO

RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer.

Project description:RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer.

| PRJNA875305 | ENA

CD271 defines a stem cell-like population in hypopharyngeal cancer.

Project description:Cancer stem cells contribute to the malignant phenotypes of a variety of cancers, but markers to identify human hypopharyngeal cancer (HPC) stem cells remain poorly understood. Here, we report that the CD271(+) population sorted from xenotransplanted HPCs possesses an enhanced tumor-initiating capability in immunodeficient mice. Tumors generated from the CD271(+) cells contained both CD271(+) and CD271(-) cells, indicating that the population could undergo differentiation. Immunohistological analyses of the tumors revealed that the CD271(+) cells localized to a perivascular niche near CD34(+) vasculature, to invasive fronts, and to the basal layer. In accordance with these characteristics, a stemness marker, Nanog, and matrix metalloproteinases (MMPs), which are implicated in cancer invasion, were significantly up-regulated in the CD271(+) compared to the CD271 (-) cell population. Furthermore, using primary HPC specimens, we demonstrated that high CD271 expression was correlated with a poor prognosis for patients. Taken together, our findings indicate that CD271 is a novel marker for HPC stem-like cells and for HPC prognosis.

| S-EPMC3633921 | biostudies-literature

RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer [dataset 1]

Project description:RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer [dataset 1]

| PRJNA875319 | ENA

RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer [dataset 2]

Project description:RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer [dataset 2]

| PRJNA875321 | ENA

CD271 regulates the proliferation and motility of hypopharyngeal cancer cells.

Project description:CD271 (p75 neurotrophin receptor) plays both positive and negative roles in cancer development, depending on the cell type. We previously reported that CD271 is a marker for tumor initiation and is correlated with a poor prognosis in human hypopharyngeal cancer (HPC). To clarify the role of CD271 in HPC, we established HPC cell lines and knocked down the CD271 expression using siRNA. We found that CD271-knockdown completely suppressed the cells' tumor-forming capability both in vivo and in vitro. CD271-knockdown also induced cell-cycle arrest in G0 and suppressed ERK phosphorylation. While treatment with an ERK inhibitor only partially inhibited cell growth, CDKN1C, which is required for maintenance of quiescence, was strongly upregulated in CD271-depleted HPC cells, and the double knockdown of CD271 and CDKN1C partially rescued the cells from G0 arrest. In addition, either CD271 depletion or the inhibition of CD271-RhoA signaling by TAT-Pep5 diminished the in vitro migration capability of the HPC cells. Collectively, CD271 initiates tumor formation by increasing the cell proliferation capacity through CDKN1C suppression and ERK-signaling activation, and by accelerating the migration signaling pathway in HPC.

| S-EPMC4965829 | biostudies-other

Pituitary tumors contain a side population with 'tumor stem cell'-associated characteristics.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-08-04 | E-GEOD-62960 | biostudies-arrayexpress

Gene expression Classification of Colon Cancer defines six molecular subtypes with distinct clinical, molecular and survival characteristics

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-05-22 | E-GEOD-40967 | biostudies-arrayexpress