Innate Sensing through Mesenchymal TLR4/MyD88 Signals Promotes Spontaneous Intestinal Tumorigenesis

Koliaraki, Vasiliki; Chalkidi, Niki; Henriques, Ana; Tzaferis, Christos; Polykratis, Apostolos; Waisman, Ari; Müller, Werner; Hackam, David J.; Pasparakis, Manolis; Kollias, George

doi:10.1016/j.celrep.2018.12.072

Cited by 40 publications

(38 citation statements)

References 37 publications

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“…Accordingly, IL-1α, a danger signal expressed by cancer cells, activates inflammatory CAFs in pancreatic ductal adenocarcinoma (PDAC) through the JAK-STAT pathway and is antagonized by TGF-β 115 . In addition, other cytokines, as well as innate immune stimuli, have been recently shown to contribute significantly to CAF activation [116][117][118] . In particular, we recently showed that TLR4 and MyD88 activation in intestinal mesenchymal cells and CAFs leads to the production of effector cytokines and chemokines, which regulate tumor cell proliferation and immune infiltration to promote intestinal cancer 116 .…”

Section: Mesenchymal Cells In Cancermentioning

confidence: 99%

The mesenchymal context in inflammation, immunity and cancer

et al. 2020

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Mesenchymal cells are mesoderm-derived stromal cells that are best known for providing structural support to organs, synthesizing and remodeling the extracellular matrix (ECM) and regulating development, homeostasis and repair of tissues. Recent detailed mechanistic insights into the biology of fibroblastic mesenchymal cells have revealed they are also significantly involved in immune regulation, stem cell maintenance and blood vessel function. It is now becoming evident that these functions, when defective, drive the development of complex diseases, such as various immunopathologies, chronic inflammatory disease, tissue fibrosis and cancer. Here, we provide a concise overview of the contextual contribution of fibroblastic mesenchymal cells in physiology and disease and bring into focus emerging evidence for both their heterogeneity at the single-cell level and their tissue-specific, spatiotemporal functional diversity.

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Section: Mesenchymal Cells In Cancermentioning

confidence: 99%

The mesenchymal context in inflammation, immunity and cancer

et al. 2020

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“…Song, Liu, & Yu, 2020). On the contrary, Toll‐like receptor 4 (TLR4)/MyD88 plays a significant role in inflammation and enhances the malignancy and proliferation of different cancers (Ding, Peng, Ding, & Peng, 2019; Koliaraki et al, 2019). Both EGFR and TLR4 can act as upstream mediators to stimulate epithelial‐to‐mesenchymal transition (EMT) in cancer cells, leading to their malignant behavior (Y. Cao, Shen, Zhang, Zhang, & Zhang, 2019; Shao et al, 2019).…”

Section: Curcumin and Lung Cancermentioning

confidence: 99%

Versatile role of curcumin and its derivatives in lung cancer therapy

Ashrafizadeh

Najafi

Makvandi

et al. 2020

Journal Cellular Physiology

101

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Lung cancer is a main cause of death all over the world with a high incidence rate. Metastasis into neighboring and distant tissues as well as resistance of cancer cells to chemotherapy demand novel strategies in lung cancer therapy. Curcumin is a naturally occurring nutraceutical compound derived from Curcuma longa (turmeric) that has great pharmacological effects, such as anti‐inflammatory, neuroprotective, and antidiabetic. The excellent antitumor activity of curcumin has led to its extensive application in the treatment of various cancers. In the present review, we describe the antitumor activity of curcumin against lung cancer. Curcumin affects different molecular pathways such as vascular endothelial growth factors, nuclear factor‐κB (NF‐κB), mammalian target of rapamycin, PI3/Akt, microRNAs, and long noncoding RNAs in treatment of lung cancer. Curcumin also can induce autophagy, apoptosis, and cell cycle arrest to reduce the viability and proliferation of lung cancer cells. Notably, curcumin supplementation sensitizes cancer cells to chemotherapy and enhances chemotherapy‐mediated apoptosis. Curcumin can elevate the efficacy of radiotherapy in lung cancer therapy by targeting various signaling pathways, such as epidermal growth factor receptor and NF‐κB. Curcumin‐loaded nanocarriers enhance the bioavailability, cellular uptake, and antitumor activity of curcumin. The aforementioned effects are comprehensively discussed in the current review to further direct studies for applying curcumin in lung cancer therapy.

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“…Interestingly, IL-1β was recently shown to drive the activation of subsets of PDGFRα + fibroblasts, contributing thus to EGF-dependent serrated polyp formation in the mouse cecum (He et al, 2019). In contrast, in vivo deletion of IL-1R1 in ColVI Cre+ mesenchymal cells had no effect in either Apc-driven spontaneous or inflammation-induced intestinal carcinogenesis (Koliaraki et al, 2019). These studies highlight both the diverse and opposing roles of IL-1 agonists in cancer and their potential distinct functions in different fibroblast or CAF subpopulations (Voronov et al, 2013).…”

Section: Fibroblast Reprogramming: Types and Underlying Molecular Mecmentioning

confidence: 99%

Fibroblast Reprogramming in Gastrointestinal Cancer

Melissari

Chalkidi

Sarris

et al. 2020

Front. Cell Dev. Biol.

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Gastrointestinal cancers are a significant cause of cancer mortality worldwide and have been strongly linked with chronic inflammation. Current therapies focus on epithelial/cancer cells; however, the importance of the tumor microenvironment in the development and treatment of the disease is also now well established. Cancerassociated fibroblasts (CAFs) are a major component of the tumor microenvironment, and are actively participating in tumor initiation, promotion and metastasis. They structurally and functionally affect cancer cell proliferation, tumor immunity, angiogenesis, extracellular matrix remodeling and metastasis through a variety of signaling pathways. CAFs originate predominantly from resident mesenchymal cells, which are activated and reprogrammed in response to cues from cancer cells. In recent years, chronic inflammation of the gastrointestinal tract has also proven an important driver of mesenchymal cell activation and subsequent CAF development, which in turn are capable of regulating the transition from acute to chronic inflammation and cancer. In this review, we will provide a concise overview of the mechanisms that drive fibroblast reprogramming in cancer and the recent advances on the downstream signaling pathways that regulate the functional properties of the activated mesenchyme. This new mechanistic insight could pave the way for new therapeutic strategies and better prognosis for cancer patients.

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Innate Sensing through Mesenchymal TLR4/MyD88 Signals Promotes Spontaneous Intestinal Tumorigenesis

Cited by 40 publications

References 37 publications

The mesenchymal context in inflammation, immunity and cancer

The mesenchymal context in inflammation, immunity and cancer

Versatile role of curcumin and its derivatives in lung cancer therapy

Fibroblast Reprogramming in Gastrointestinal Cancer

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