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

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE212397 | GEO | 2022/10/26

REPOSITORIES: GEO

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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.

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 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

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

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-10-26 | GSE212399 | GEO

Genome-wide analysis of human bone marrow CD45-CD271+ cells in comparision with CD45-CD271- cells

Project description:Analyze and compare the gene expression profile of human bone marrow primary CD45-CD271+ and CD45-CD271- cells. The hypothesis was some genes were differentially expressed in these two populations. Results provided important information regarding the gene expression difference of these two cell populations.

2015-03-17 | GSE57927 | GEO

Expresson of CD271 HIGH and LOW populations in melanoma cells during invasion

Project description:Human engeneered skin carrying GFP positive melanoma cells was transplanted in immunocompromised rats. 6 weeks after transplatation the engeenered skin was removed and GFP positive melanoma cells sorted for CD271 HIGH and LOW populations

2017-09-02 | GSE103382 | GEO

CD271 is preferentially expressed and essential for cell proliferation in squamous cell carcinoma of the lung

Project description:Squamous cell carcinoma is a major type of cancer in the lung. While several therapeutic target molecules for lung adenocarcinoma have been identified, little is known about lung squamous cell carcinoma (LSCC). We recently reported that CD271 (p75 neurotrophin receptor) serves as a marker for tumor initiation and is a key regulator of cell proliferation in hypopharyngeal squamous cell carcinoma. In this study, we found that CD271 was also expressed in squamous cell carcinoma, but not in adenocarcinoma, of several tissues, including the lung. To examine CD271’s role in LSCC, we established xenograft cell lines from LSCC patients. Within the sorted live LSCC cell population, the CD271high cells were primarily cycling through the G2/M phase, while the CD271low cells were mostly in the G0 phase. CD271 knockdown in the LSCC cells completely suppressed their proliferation and tumor-formation capability, and increased their cell-cycle arrest in the G0 phase. In the CD271-knockdown cells, ERK-phosphorylation was decreased, while no change was observed in the IκBα-, p65-, or Akt-phosphorylation. Treatment with the MEK inhibitor U0126 decreased the LSCC cells’ proliferation capability. Microarray analysis revealed that CD271 knockdown attenuated the RAS-related pathways. The knockdown of TrkB, which forms a heterodimer with CD271 and accelerates its downstream signaling, partially inhibited the LSCC cell proliferation. These results indicated that LSCC exclusively depends on CD271 for cell proliferation, in part through ERK-signaling activation.

2021-08-06 | GSE118141 | GEO

Identification of a CD271-associated signaling network in human malignant melanoma cells

Project description:Background: Large-scale genomic analyses of patient cohorts have revealed extensive heterogeneity between individual tumors, contributing to treatment failure and drug resistance. In malignant melanoma, heterogeneity is thought to arise as a consequence of the differentiation of melanoma-initiating cells that are defined by cell-surface markers like CD271 or CD133. Results: Here we identified the nerve growth factor receptor (CD271) as a crucial determinant of melanoma cell tumorigenicity, stem-like properties, heterogeneity and plasticity. Stable shRNA mediated knock-down of CD271 in patient-derived melanoma cells abrogated their tumor-initiating and colony-forming capacity. A genome-wide expression profiling and gene-set enrichment analysis revealed novel connections of CD271 with melanoma-associated genes like CD133 and points to a neural crest stem cell (NCSC) signature lost upon CD271 knock-down. In a meta-analysis, we found CD271 linked to the neural crest specifier SOX10 and observed a shared set of 271 differentially regulated genes. To dissect the connection of CD271 and CD133 we analyzed 10 patient-derived melanoma-cell lines for cell-surface expression of both markers compared to established cell lines MeWo and A375. We found CD271+ cells in the majority of cell lines analyzed as well as in a set of 16 different patient-derived melanoma metastases. Strikingly, only 2/12 cell lines harbored a CD133+ sub-set that in addition comprised a fraction of cells of a CD271+/CD133+ phenotype. Those cells were found in the label-retaining fraction and in vitro deduced from CD271+ but not CD271 knock-down cells. Conclusions: Our present study provides a deeper insight into the regulation of melanoma cell properties and points CD271 out as a regulator of several melanoma-associated genes. Further, our data strongly suggest CD271 is a crucial determinant of stem-like properties of melanoma cells like colony-formation and tumorigenicity.

2013-11-19 | GSE52456 | GEO

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