Evidence map›Paper›PMID 39030572›Full record

ArticleJournal of experimental & clinical cancer research : CR2024

TSP50 facilitates breast cancer stem cell-like properties maintenance and epithelial-mesenchymal transition via PI3K p110α mediated activation of AKT signaling pathway.

Feng Gao, Sichen Liu, Jing Wang, Gang Wei, Chunlei Yu, Lihua Zheng, Luguo Sun, Guannan Wang, Ying Sun, Yongli Bao and 1 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Feng GaoNational Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, NO.5268 Renmin Street, Changchun, 130117, China.
Sichen LiuDepartment of Neurosurgery/Neuro-Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, China.
Jing WangNational Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, NO.5268 Renmin Street, Changchun, 130117, China.
Gang WeiDepartment of Breast Surgery, Jilin Province Cancer Hospital, Changchun, 130012, China.
Chunlei YuNational Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, NO.5268 Renmin Street, Changchun, 130117, China.
Lihua ZhengNMPA Key Laboratory for Quality Control of Cell and Gene Therapy Medicine Products, Northeast Normal University, NO.5268 Renmin Street, Changchun, 130117, China.
Luguo SunNational Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, NO.5268 Renmin Street, Changchun, 130117, China.
Guannan WangChina International Joint Research Center for Human Stem Cell Bank, Northeast Normal University, Changchun, Jilin, 130024, China.
Ying SunChina International Joint Research Center for Human Stem Cell Bank, Northeast Normal University, Changchun, Jilin, 130024, China.
Yongli BaoNMPA Key Laboratory for Quality Control of Cell and Gene Therapy Medicine Products, Northeast Normal University, NO.5268 Renmin Street, Changchun, 130117, China. baoyl800@nenu.edu.cn.
Zhenbo SongNational Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, NO.5268 Renmin Street, Changchun, 130117, China. songzb484@nenu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundStudies have confirmed that epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties are conducive to cancer metastasis. In recent years, testes-specific protease 50 (TSP50) has been identified as a prognostic factor and is involved in tumorigenesis regulation. However, the role and molecular mechanisms of TSP50 in EMT and CSC-like properties maintenance remain unclear.

methodsThe expression and prognostic value of TSP50 in breast cancer were excavated from public databases and explored using bioinformatics analysis. Then the expression of TSP50 and related genes was further validated by quantitative RT-PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC). In order to investigate the function of TSP50 in breast cancer, loss- and gain-of-function experiments were conducted, both in vitro and in vivo. Furthermore, immunofluorescence (IF) and immunoprecipitation (IP) assays were performed to explore the potential molecular mechanisms of TSP50. Finally, the correlation between the expression of TSP50 and related genes in breast cancer tissue microarray and clinicopathological characteristics was analyzed by IHC.

resultsTSP50 was negatively correlated with the prognosis of patients with breast cancer. TSP50 promoted CSC-like traits and EMT in both breast cancer cells and mouse xenograft tumor tissues. Additionally, inhibition of PI3K/AKT partly reversed TSP50-induced activation of CSC-like properties, EMT and tumorigenesis. Mechanistically, TSP50 and PI3K p85α regulatory subunit could competitively interact with the PI3K p110α catalytic subunit to promote p110α enzymatic activity, thereby activating the PI3K/AKT signaling pathway for CSC-like phenotypes maintenance and EMT promotion. Moreover, IHC analysis of human breast cancer specimens revealed that TSP50 expression was positively correlated with p-AKT and ALDH1 protein levels. Notably, breast cancer clinicopathological characteristics, such as patient survival time, tumor size, Ki67, pathologic stage, N stage, estrogen receptor (ER) and progesterone receptor (PR) levels, correlated well with TSP50/p-AKT/ALDH1 expression status.

conclusionThe effects of TSP50 on EMT and CSC-like properties promotion were verified to be dependent on PI3K p110α. Together, our study revealed a novel mechanism by which TSP50 facilitates the progression of breast cancer, which can provide new insights into TSP50-based breast cancer treatment strategies.

Indexed as

Breast NeoplasmsEpithelial-Mesenchymal TransitionNeoplastic Stem CellsProto-Oncogene Proteins c-aktSignal TransductionAnimalsCell Line, TumorCell ProliferationFemaleHumansMiceMice, NudePhosphatidylinositol 3-KinasesPrognosisSerine EndopeptidasesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSerine Endopeptidasestestis-specific protease 50Breast cancerCSC-like propertiesEMTPI3K/AKT pathwayTSP50

Identifiers

PMID39030572
PMCPMC11264956

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.