Evidence map›Paper›PMID 42624900›Full record

ArticleOncogene2026

PTEN-AKT2 regulates mixed lineage liver cancer development and sensitizes cancer cells to TGFβ treatment.

Qi Tang, Ielyzaveta Slarve, Jingyu Chen, Ni Zeng, Yiwei Gu, Lina He, Shunan Hu, Diala Alhousari, Zifei Xu, Brittney Hua and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Qi TangPharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA.
Ielyzaveta SlarvePharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA.
Jingyu ChenPharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA.
Ni ZengPharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA.
Yiwei GuPharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA.
Lina HePharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA.
Shunan HuPharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA.
Diala AlhousariPharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA.
Zifei XuPharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA.
Brittney HuaPharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA.
Guo ZhangPharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA.
Phillip NguyenPharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA.
Mario AlbaMedicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
Ajay BharadwajBiomedical Sciences, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
Jihyeon LeeBiomedical Sciences, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
Simion KreimerBiomedical Sciences, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
Jian XuCenter for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA.
Baoan JiCancer Biology, Mayo Clinic, Jacksonville, FL, 32224, USA.
Shelly C LuKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
Jennifer Van EykBiomedical Sciences, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
Shefali ChopraDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Gary KanelDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Liyun YuanDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Bangyan L StilesPharmacology and Pharmaceutical Sciences, Mann School of Pharmacy, University of Southern California, Los Angeles, CA, 90033, USA. bstiles@usc.edu.ORCID http://orcid.org/0000-0001-5480-2074

Funding

The role of PTEN and AKT2 in the malignant transformation of liver progenitor celR01CA154986 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI STILES, BANGYAN · 2013 to 2017
$1.7M
The Role of ERRa in liver lipid dysfunction and pathologyR01DK131492 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI STILES, BANGYAN · 2022 to 2025
$1.5M
NCI NIH HHS R01 CA154986NIDDK NIH HHS R01 DK131492U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA154986U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK131492
6 · The paper itself

Abstract

Primary liver cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), arise from the neoplastic transformation of hepatocytes and cholangiocytes, respectively. Loss or downregulation of PTEN, a tumor suppressor negatively regulating the PI3K/AKT pathway, is frequently observed in CCA and HCC. Notably, PTEN mutations are observed at nearly twice the frequency in combined CCA-HCC tumors than either HCC or CCA alone. Using lineage-specific liver-targeted PTEN-deficient mouse models, we demonstrate that PTEN loss drives cellular dedifferentiation and tumorigenesis, a process that is critically dependent on AKT2. Mechanistically, PTEN deficiency induces activation of NOTCH and upregulation of transcriptional factor SOX9, which plays a central role in tumor cell transformation. In parallel, PTEN loss increases SMAD4 expression and sensitizes the tumor cells to TGFβ signaling, with TGFβ treatment repressing SOX9 expression in tumor cells lacking PTEN. Together, our study defined a critical role for PTEN-AKT2 signaling in maintaining liver epithelial lineage fidelity and revealed how its disruption promotes the conversion of mature hepatocytes or cholangiocytes into liver cancer stem-like cells (LCSCs). Furthermore, we identify a PTEN-dependent crosstalk between NOTCH and TGFβ pathways that governs liver tumor development. Together, this work provides mechanistic insight into lineage plasticity in liver cancer with implications for pathway-directed therapy.

Indexed as

Carcinoma, HepatocellularCholangiocarcinomaLiver NeoplasmsProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseTransforming Growth Factor betaAnimalsCell LineageCell Transformation, NeoplasticGene Expression Regulation, NeoplasticHepatocytesHumansMiceMice, KnockoutNeoplastic Stem CellsReceptors, NotchAkt2 protein, mouseProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePten protein, mouseReceptors, NotchSmad4 ProteinSmad4 protein, mouseSox9 protein, mouseSOX9 Transcription FactorTransforming Growth Factor beta

Identifiers

PMID42624900
PMCPMC13645676

What Socratic holds

Textmetadata
Read underepoch 390

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.