<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "TGF-β induced chemoresistance in liver cancer is modulated by xenobiotic nuclear receptor PXR."^^ . "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. HCC: Hepatocellular Carcinoma; FDA: Food and Drug Administration; TGF-β: Transforming growth factor-β; PXR: Pregnane X receptor; CAR: Constitutive androstane receptor; P-gp/ABCB1: P-glycoproteins/ATP-binding cassette transporter subfamily B member 1; MRP1/ABCC1 and MRP2/ABCC2: Multidrug-resistance associated proteins; BCRP/ABCG2: Breast cancer resistant protein; DMEs: Drug-metabolizing enzymes; CFDA: 5,6-carboxyfluorescein diacetate; ETS1: Transcription factor E26 transformation specific sequence 1."^^ . "2019-12" . "18" . "24" . . "Taylor& Francis "^^ . . . "Cell cycle (Georgetown, Tex.)"^^ . . . "15514005" . . . . . . . . . . . . . . . . . . . . . . . . . "Drishti"^^ . "Tiwari"^^ . "Drishti Tiwari"^^ . . "Sumit"^^ . "Kumar"^^ . "Sumit Kumar"^^ . . "Pawan"^^ . "Gupta"^^ . "Pawan Gupta"^^ . . "Nancy"^^ . "Ahuja"^^ . "Nancy Ahuja"^^ . . "Ella"^^ . "Bhagyaraj"^^ . "Ella Bhagyaraj"^^ . . "Ravikanth"^^ . "Nanduri"^^ . "Ravikanth Nanduri"^^ . . "Shalini"^^ . "Gupta"^^ . "Shalini Gupta"^^ . . . . . "HTML Summary of #2507 \n\nTGF-β induced chemoresistance in liver cancer is modulated by xenobiotic nuclear receptor PXR.\n\n" . "text/html" . . . "QR Microbiology"@en . .