MRTF-A-NF-κB/p65 axis-mediated PDL1 transcription and expression contributes to immune evasion of non-small-cell lung cancer via TGF-β

Du, Fu; Qi, Xin; Zhang, Aotong; Wang, Xuemin; Proud, Christopher G.; Lin, Chang-Shen; Fan, Xinglong; Li, Jing

doi:10.1038/s12276-021-00670-3

Cited by 29 publications

(24 citation statements)

References 59 publications

(74 reference statements)

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“…In this axis, Myocardin-related transcription factor-A (MRTF-A) plays an immune suppressive function. Rho/ROCK signaling is involved in the noncanonical pathway to suppress TGF-β induced PD-L1 expression, contributing the translocation of MRTF-A to the nucleus [ 140 ].…”

Section: Rock and Cancer Immunotherapymentioning

confidence: 99%

Rho-Kinase as a Target for Cancer Therapy and Its Immunotherapeutic Potential

Kim

Han

et al. 2021

IJMS

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Cancer immunotherapy is fast rising as a prominent new pillar of cancer treatment, harnessing the immune system to fight against numerous types of cancer. Rho-kinase (ROCK) pathway is involved in diverse cellular activities, and is therefore the target of interest in various diseases at the cellular level including cancer. Indeed, ROCK is well-known for its involvement in the tumor cell and tumor microenvironment, especially in its ability to enhance tumor cell progression, migration, metastasis, and extracellular matrix remodeling. Importantly, ROCK is also considered to be a novel and effective modulator of immune cells, although further studies are needed. In this review article, we describe the various activities of ROCK and its potential to be utilized in cancer treatment, particularly in cancer immunotherapy, by shining a light on its activities in the immune system.

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Section: Rock and Cancer Immunotherapymentioning

confidence: 99%

Rho-Kinase as a Target for Cancer Therapy and Its Immunotherapeutic Potential

Kim

Han

et al. 2021

IJMS

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“…In line with this, ROCK-mediated moesin phosphorylation regulated the PD-L1 stability by preventing its degradation in breast cancer cells [121]. In non-small cell lung cancer cells, TGF-β signaling upregulated the expression of MRTF (through a RhoA/ROCK non-canonical mechanism), which interacted with NF-κB/p65 to promote PD-L1 expression through transcription [122]. Whether these mechanisms occur in melanoma and their importance in the context of therapy resistance remain to be investigated.…”

Section: Perspective and Unanswered Questionsmentioning

confidence: 63%

Cytoskeletal Remodelling as an Achilles’ Heel for Therapy Resistance in Melanoma

Barreno

2022

Cells

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Melanoma is an aggressive skin cancer with a poor prognosis when diagnosed late. MAPK-targeted therapies and immune checkpoint blockers benefit a subset of melanoma patients; however, acquired therapy resistance inevitably arises within a year. In addition, some patients display intrinsic (primary) resistance and never respond to therapy. There is mounting evidence that resistant cells adapt to therapy through the rewiring of cytoskeleton regulators, leading to a profound remodelling of the actomyosin cytoskeleton. Importantly, this renders therapy-resistant cells highly dependent on cytoskeletal signalling pathways for sustaining their survival under drug pressure, which becomes a vulnerability that can be exploited therapeutically. Here, we discuss the current knowledge on cytoskeletal pathways involved in mainly targeted therapy resistance and future avenues, as well as potential clinical interventions.

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“…MRTFA is strongly associated with cell viability of its correlation with cytoskeleton and actin ( 33 ). It has been identified as an EMT and metastasis regulator in NPC ( 34 ) and NSCLC ( 35 ). BTBD10 functions as an activator of AKT family members by inhibiting PPP2CA-mediated dephosphorylation, and a few studies have identified it as a prognostic risk factor in hepatocellular carcinoma ( 36 ) and glioma ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis signature and PLCD3 predicts immune infiltration and drug responses in osteosarcoma

Yin

Jiang

et al. 2023

Front. Oncol.

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Osteosarcoma (OS) is a cancer that is frequently found in children and adolescents and has made little improvement in terms of prognosis in recent years. A recently discovered type of programmed cell death called cuproptosis is mediated by copper ions and the tricarboxylic acid (TCA) cycle. The expression patterns, roles, and prognostic and predictive capabilities of the cuproptosis regulating genes were investigated in this work. TARGET and GEO provided transcriptional profiling of OS. To find different cuproptosis gene expression patterns, consensus clustering was used. To identify hub genes linked to cuproptosis, differential expression (DE) and weighted gene co-expression network analysis (WGCNA) were used. Cox regression and Random Survival Forest were used to build an evaluation model for prognosis. For various clusters/subgroups, GSVA, mRNAsi, and other immune infiltration experiments were carried out. The drug-responsive study was carried out by the Oncopredict algorithm. Cuproptosis genes displayed two unique patterns of expression, and high expression of FDX1 was associated with a poor outcome in OS patients. The TCA cycle and other tumor-promoting pathways were validated by the functional study, and activation of the cuproptosis genes may also be connected with immunosuppressive state. The robust survival prediction ability of a five-gene prognostic model was verified. This rating method also took stemness and immunosuppressive characteristics into account. Additionally, it can be associated with a higher sensitivity to medications that block PI3K/AKT/mTOR signaling as well as numerous chemoresistances. U2OS cell migration and proliferation may be encouraged by PLCD3. The relevance of PLCD3 in immunotherapy prediction was verified. The prognostic significance, expressing patterns, and functions of cuproptosis in OS were revealed in this work on a preliminary basis. The cuproptosis-related scoring model worked well for predicting prognosis and chemoresistance.

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MRTF-A-NF-κB/p65 axis-mediated PDL1 transcription and expression contributes to immune evasion of non-small-cell lung cancer via TGF-β

Cited by 29 publications

References 59 publications

Rho-Kinase as a Target for Cancer Therapy and Its Immunotherapeutic Potential

Rho-Kinase as a Target for Cancer Therapy and Its Immunotherapeutic Potential

Cytoskeletal Remodelling as an Achilles’ Heel for Therapy Resistance in Melanoma

Cuproptosis signature and PLCD3 predicts immune infiltration and drug responses in osteosarcoma

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