ArticleCell cycle (Georgetown, Tex.)2019
TGF-β induced chemoresistance in liver cancer is modulated by xenobiotic nuclear receptor PXR.
Article in Cell cycle (Georgetown, Tex.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 71 citations in OpenAlex.
- EMT and cancer stem cells: Drivers of therapy resistance and promising therapeutic targets.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2025Review
- Exosomal long non-coding RNAs in gastrointestinal cancer: chemoresistance mediators and therapeutic targets.Journal of translational medicine · 2025Review
- Role of exosomes in transforming growth factor-β-mediated cancer cell plasticity and drug resistance.Exploration of targeted anti-tumor therapy · 2025Review
- Transcription factor E2F4 facilitates SUMOylation to promote HCC progression through interaction with LIN9.International journal of oncology · 2024Article
- Nuclear receptor Rev-erbα role in fine-tuning erythropoietin gene expression.Blood advances · 2024Article
- Doxorubicin-induced chemoresistance in Duke's type B colon adenocarcinoma cell line is aggravated in the presence of TGF-β2 through non-apoptotic cell death.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Nr1h4 and Thrb ameliorate ER stress and provide protection in the MPTP mouse model of Parkinson's.Life science alliance · 2024Article
- Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- 2,2'- Bipyridine Derivatives Exert Anticancer Effects by Inducing Apoptosis in Hepatocellular Carcinoma (HepG2) Cells.Journal of hepatocellular carcinoma · 2024Article
- Immune-related lncRNAs pairs prognostic score model for prediction of survival in acute myeloid leukemia patients.Clinical and experimental medicine · 2023Article
- Advances in drug resistance of triple negative breast cancer caused by pregnane X receptor.World journal of clinical oncology · 2023Review
- Angiogenic signaling pathways and anti-angiogenic therapy for cancer.Signal transduction and targeted therapy · 2023Review
- Novel insights into the impact of liver inflammatory responses on primary liver cancer development.Liver research (Beijing, China) · 2023Review
- Article
- Noncoding RNA-mediated molecular bases of chemotherapy resistance in hepatocellular carcinoma.Cancer cell international · 2022Review
- Ets1 mediates sorafenib resistance by regulating mitochondrial ROS pathway in hepatocellular carcinoma.Cell death & disease · 2022Article
- Transcriptomic and network pharmacology approaches revealed possible mechanisms underlying the 5-fluorouracil (5-FU)-sensitizing effect of Xuan-Fu-Hua decoction treatment on liver cancer cells.Translational cancer research · 2022Article
- Bile acids and their receptors: modulators and therapeutic targets in liver inflammation.Seminars in immunopathology · 2022Review
- The functional multipotency of transforming growth factor β signaling at the intersection of senescence and cancer.Cellular and molecular life sciences : CMLS · 2022Review
- Prrx1 promotes resistance to temozolomide by upregulating ABCC1 and inducing vasculogenic mimicry in glioma.American journal of cancer research · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma appears as an extremely angiogenic solid tumor marked by apoptosis evasion, dysregulated cell cycle and low sensitivity to chemotherapy. TGF-β, a multifunctional cytokine, plays a pleiotropic role in the tumor microenvironment and has implications in cancer drug resistance. The current study provides novel evidence that TGF-β signaling contributes to drug resistance in liver cancer cells by inducing the expression of xenobiotic nuclear receptor PXR. We observed that PXR increases the expression of drug efflux transporters; therefore, accounting for exacerbated drug resistance. Additionally, anti-apoptotic nature of PXR contributes to TGF-β mediated chemoresistance as seen by procaspase-3 and Mcl-1 cellular levels. TGF-β binding to the TGF-β receptor triggers a complex downstream signaling cascade through a non-canonical SMAD-independent ERK pathway that leads to increased PXR expression. Activated ERK activates ETS1 transcription factor which is a critical regulator of endogenous PXR expression in hepatic cells. Loss of function of ETS1 abrogates the TGF-β induced PXR expression. Together these findings indicate that PXR modulates TGF-β induced resistance to chemotherapy in liver cancer cells. This underscores the need for combinatorial approaches with focus on PXR antagonism to improve drug effectiveness in hepatocellular carcinoma.
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