Evidence map›Paper›PMID 40301365›Full record

ArticleScientific reports2025

AKT1 as a therapeutic target for platinum-resistant SOX2 positive ovarian cancer cells.

Mengyang Xue, Li Kang, Yunfeng Zhang, Xixia Yuan, Jiwen Li, Rong Zhang, Jiemin Wong

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Mengyang XueThe Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China.
Li Kang *Shanghai Key Laboratory of Regulatory Biology, Fengxian District Central Hospital-ECNU Joint Center of Translational Medicine, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.
Yunfeng Zhang *Shanghai Key Laboratory of Regulatory Biology, Fengxian District Central Hospital-ECNU Joint Center of Translational Medicine, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.
Xixia YuanShanghai Key Laboratory of Regulatory Biology, Fengxian District Central Hospital-ECNU Joint Center of Translational Medicine, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.
Jiwen LiShanghai Key Laboratory of Regulatory Biology, Fengxian District Central Hospital-ECNU Joint Center of Translational Medicine, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.
Rong ZhangThe Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China. rongzhang@163.com.
Jiemin WongShanghai Key Laboratory of Regulatory Biology, Fengxian District Central Hospital-ECNU Joint Center of Translational Medicine, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China. jmweng@bio.ecnu.edu.cn.

Funding

National Natural Science Foundation of China 3173004National Natural Science Foundation of China 82203355Science and Technology Commission of Shanghai Municipality 20JC1411500
6 · The paper itself

Abstract

Ovarian cancer remains the most lethal gynecological malignancy, largely owing to its chemotherapy resistance and high recurrence rate. Emerging evidence has linked the aberrant expression of SOX2, a transcription factor that is important in the development and maintenance of stem cell state, with chemoresistance and poor prognosis of ovarian cancer patients. In this study, we aimed to elucidate the mechanisms that drive aberrant SOX2 expression in ovarian cancer cells. By examining multiple ovarian cancer cell lines and a panel of clinical tumor samples, we observed a broad overexpression of SOX2 in ovarian cancer cell lines and tumors. To identify signaling pathway(s) that drives SOX2 overexpression in ovarian cancer cells, we screened a set of small-molecule kinase inhibitors that target 30 major cellular kinases. Among the top hits identified are AKT inhibitors. We demonstrated that inhibition or knockdown of AKT1 can drastically downregulate SOX2 protein level, impairs the growth and stemness of SOX2-positive ovarian cancer cells, and markedly sensitize SOX2-positive ovarian cancer cells to platinum drugs. Mechanically, we found that AKT1 drives SOX2 overexpression primarily by enhancing its protein stability and does so by phosphorylating SOX2 at threonine 116. Altogether, our study reveals an underlying mechanism that drives SOX2 overexpression in ovarian cancer and underscores pharmacological inhibition of AKT1 as a potential therapeutic strategy to sensitize SOX2-positive ovarian cancer to platinum drugs.

Indexed as

Drug Resistance, NeoplasmOvarian NeoplasmsProto-Oncogene Proteins c-aktSOXB1 Transcription FactorsAntineoplastic AgentsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansNeoplastic Stem CellsPlatinumProtein Kinase InhibitorsSignal TransductionAKT1 protein, humanAntineoplastic AgentsPlatinumProtein Kinase InhibitorsProto-Oncogene Proteins c-aktSOX2 protein, humanSOXB1 Transcription FactorsAKT1ChemotherapyOvarian cancerProtein stabilitySOX2

Identifiers

PMID40301365
PMCPMC12041294

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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 OpenQuestion graph.