Clathrin switches transforming growth factor-β role to pro-tumorigenic in liver cancer

Caballero‐Díaz, Daniel; Bertrán, Esther; Peñuelas‐Haro, Irene; Moreno-Càceres, Joaquim; Malfettone, Andrea; López-Luque, Judit; Addante, Annalisa; Herrera, Blanca; Sánchez, Aránzazu; Alay, Ania; Solé, Xavier; Serrano, Teresa; Ramos, Emilio; Fabregat, Isabel

doi:10.1016/j.jhep.2019.09.012

Cited by 32 publications

(27 citation statements)

References 38 publications

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“…Down-regulation of CLTC attenuates TGF-β-mediated anti-apoptotic effect in hepatocytes. 36 Our study also confirmed these findings in osteosarcoma. Moreover, WB also confirmed that CLTC knockdown could inhibit the activation of AKT/mTOR signaling in osteosarcoma.…”

Section: Discussionsupporting

confidence: 87%

Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF‐beta and AKT/mTOR signaling pathways

Pan

Qin

et al. 2021

Clinical & Translational Med

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1. High CLTC expression is associated with worse clinical outcomes in osteosarcoma patients. 2. Inhibition of CLTC suppresses osteosarcoma growth both in vitro and in vivo.3. SP1 binds to the CLTC promoter to promote the transcriptional activity of CLTC in osteosarcoma. 4. CLTC-mediated oncogenic effects occurred through activation of the TGF-beta and AKT/mTOR signaling pathway in a TFG-dependent manner.

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Section: Discussionsupporting

confidence: 87%

Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF‐beta and AKT/mTOR signaling pathways

Pan

Qin

et al. 2021

Clinical & Translational Med

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“…EMT is majorly influenced by change in several genes expression, in which TGFβ plays a major role by inducing metabolic reprogramming. Our gene-expression studies showed that TGF-β and its downstream target RhoA are both up-regulated when treated with AN extract [ 40 , 41 , 42 ]. TGF-β signaling is known to reduce cell migration by upregulating expression of Snail and Slug [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…This was further confirmed by incubating AN-treated cells with ALK5, which inhibits TGF-β. AN-treated cells treated with ALK5 showed higher cell viability compared to AN-treated cells [ 40 , 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor effects of Artemisia nilagirica extract on MDA-MB-231 breast cancer cells: deciphering the biochemical and biomechanical properties via TGF-β upregulation

Raju

Balakrishnan

Kollimada

et al. 2020

Heliyon

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Purpose Artemisia nilagirica (AN), which is known to have antimicrobial, antioxidant, antiulcer, and anti-asthmatic properties, has been recently shown to have anti-cancer activity. However, the mechanism responsible for the anti-cancer property and its effect on cellular properties and functions are not known. Material and methods We have characterized the biochemical and biomechanical properties of MDA-MB-231 cells treated with the methanolic extract from AN. Results We show that AN-treatment decreases cell-eccentricity, increases expression of actin and microtubules, and do not affect cell-area. Increased expression of cytoskeletal proteins is known to change the mechanical properties of the cells, which was confirmed using micropipette aspiration and Atomic Force Microscopy. We identified the upregulation of the tumorigenic pathway (TGF-β) leading to activation of Rho-A as the molecular mechanism responsible for actin upregulation. Since the initial stages of TGF-β upregulation are known to suppress tumor growth by activating apoptosis, we hypothesized that the mechanism of cell death due to AN-treatment is through TGF-β activation. We have validated this hypothesis by partially recuing cell death through inhibition of TGF-β using Alk-5. Conclusion In summary, our study reveals the mechanism of action of Artemisia nilagirica using a synergy between biochemical and biomechanical techniques.

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“…In their findings, knockdown of clathrin could not affect phosphorylation of SMAD2, while the suppression of EGFR and AKT phosphorylation was observed. These results indicated that SMAD-independent pathway was involved in transactivation of EGFR [51]. Moreover, TGF-β signaling has been found to activate p38/JNK through TGF-β-activated kinase 1 (TAK1) and Mixed Lineage Kinase 3 (MLK3) in a non-SMAD pathway, holding the balance in cell fate [52,53].…”

Section: Tgf-β Signaling Pathway and Its Function In Hccmentioning

confidence: 94%

Modulation of the TGF-β signaling pathway by long noncoding RNA in hepatocellular carcinoma

et al. 2020

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Hepatocellular carcinoma (HCC) is a type of liver cancer with poor prognosis. There have been demonstrated to exist many possible mechanisms in HCC tumorigenesis, and recent investigations have provided some promising therapy targets. However, further mechanisms remain to be researched to improve the therapeutic strategy and diagnosis of HCC. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine which plays critical roles in networks of different cellular processes, and TGF-β signaling has been found to participate in tumor initiation and development of HCC in recent years. Moreover, among the molecules and signaling pathways, researchers paid more attention to lncRNAs (long non-coding RNAs), but the connection between lncRNAs and TGF-βremain poorly understood. In this review, we conclude the malignant procedure which lncRNAs and TGF-β involved in, and summarize the mechanisms of lncRNAs and TGF-βin HCC initiation and development. Furthermore, the interaction between lncRNA and TGF-β are paid more attention, and the potential therapy targets are mentioned.

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Clathrin switches transforming growth factor-β role to pro-tumorigenic in liver cancer

Cited by 32 publications

References 38 publications

Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF‐beta and AKT/mTOR signaling pathways

Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF‐beta and AKT/mTOR signaling pathways

Anti-tumor effects of Artemisia nilagirica extract on MDA-MB-231 breast cancer cells: deciphering the biochemical and biomechanical properties via TGF-β upregulation

Modulation of the TGF-β signaling pathway by long noncoding RNA in hepatocellular carcinoma

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