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Series GSE270578 Query DataSets for GSE270578
Status Public on Jul 30, 2024
Title TFCP2L1 promotes GPX4-mediated ferroptosis to inhibit breast cancer cell proliferation and metastasis via the PI3K/AKT signaling pathway
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Breast cancer represents the most prevalent form of malignant tumors among women. Despite the existence of numerous therapeutic methods, a significant portion of patients face a poor prognosis, highlighting the urgency in identifying new remedial targets. Here, we for the first time demonstrated that the CP2 family member TFCP2L1, a classical marker of embryonic stem cell maintenance, as a tumor suppressor in breast cancer. Patients with breast cancer have poorer prognoses when TFCP2L1 is expressed highly. Consistently, the expression of TFCP2L1 is higher in normal breast cells than those in breast cancer cell lines. Gain- and loss-of-function and xenograft tumor assay showed that overexpression of TFCP2L1 significantly inhibited both the proliferation and migration of breast cancer cells in vivo and in vitro. Conversely, the knockdown of TFCP2L1 promoted the proliferation and migration of breast cancer cells. Mechanistically, we found that TFCP2L1 suppresses breast cancer progression by directly inhibiting the expression of glutathione peroxidase 4 (GPX4), a key regulator of ferroptosis. Therefore, inhibition of GPX4 by RSL3, an inducer of ferroptosis was able to promote the function of TFCP2L1 in breast cancer cells. On the other hand, transcriptome high-throughput exhibited that TFCP2L1 negatively regulated the activity of PI3K/AKT signaling pathway. Administration of SC79, an AKT activator, was capable of partially restoring the negative effects of TFCP2L1 on GPX4 transcription. Together, TFCP2L1 functions by directly or indirectly regulating GPX4-mediated ferroptosis, and may serve as a novel biomarker and potential therapeutic target for breast cancer.
 
Overall design Empty control group of Hs578T cells and the Hs578T cells with overexpression of TFCP2L1 were collected by using Trizol. Two repeat groups were set for each treatment group. These samples were sent to MajorBIO (Shanghai, China) company to do deep sequencing by using illumina Hiseq.
 
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Submission date Jun 24, 2024
Last update date Jul 30, 2024
Contact name shoudong ye
Organization name Anhui University
Department Cell Biology
Street address No 111, Jiu Long Road
City Hefei
ZIP/Postal code 230601
Country China
 
Platforms (1)
GPL34284 Illumina NovaSeq X Plus (Homo sapiens)
Samples (4)
GSM8347660 HPB_1
GSM8347661 HPB_2
GSM8347662 Hh_3
Relations
BioProject PRJNA1127507

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Supplementary file Size Download File type/resource
GSE270578_FLAG_vs_TFCP2L1.deseq2.xlsx 15.9 Mb (ftp)(http) XLSX
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