Myeloid Differentiation Primary Response 88–Cyclin D1 Signaling in Breast Cancer Cells Regulates Toll-Like Receptor 3-Mediated Cell Proliferation

Singh, Aradhana; Devkar, Ranjitsinh; Basu, Anupam

doi:10.3389/fonc.2020.01780

Cited by 5 publications

(3 citation statements)

References 52 publications

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“…These results demonstrate that suppression of AQP7 is essential for inhibiting cell cycle arrest in ccRCC. A previous study indicated that PPARα-de cient mice showed accelerated cell regeneration and increased cyclin D1 protein levels [34], and the NF-κB signaling pathway induces and regulates cyclin D1 [35]. Another crucial biological function of PPARα is the suppression of in ammation [36], and in ammation has been identi ed as a pivotal oncogenesis event induced by sustaining HIF activation in ccRCC [37].…”

Section: Discussionmentioning

confidence: 99%

Suppression of AQP7 is Crucial for Proliferation and Lipid Metabolism in ccRCC

Zhao,

Wang,

Jin

et al. 2024

Preprint

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Background: It is well-established that reprogramming of lipid metabolism is a feature of clear cell renal cell carcinoma (ccRCC), which also acts as a driving force in oncogenesis induced by hypoxia-inducible factors (HIFs) in ccRCC. Aquaporin 7 (AQP7), a channel facilitates glycerol to pass through the membrane and induces a decrease in triglycerides (TGs) and glycerol in adipocytes. However, whether AQP7 takes a part in the lipid metabolism and malignant behaviors of ccRCC is still unclear. Methods: The prognosis and diagnostic value of AQP7 in ccRCC were first evaluated by bioinformatics methods including TCGA database, Cox regression, etc. The expression of AQP7 was tested with tissue microarray and IHC. After AQP7 was stably upregulated by lentivirus transfection, cell viability, colony formation, and flow cytometry were performed. According to GSEA, Nile red staining was then used to detect lipid droplet accumulation, and relevant mechanisms and pathways were verified through Western blotting and qPCR. Results: AQP7 was suppressed in both TCGA and the tissue microarray cohort, and the prognosis was worse for patients with lower AQP7 levels, including OS, DSS and PFI. Multiple lipid metabolism pathways, especially the PPARα pathway, were activated in the cohort with high AQP7 expression based on gene set enrichment analysis (GSEA). Moreover, AQP7 overexpression in ccRCC inhibited the proliferation ability, reduced the TG and glycerol contents, and led to cell cycle arrest. As a crucial transcription factor relevant to lipid metabolism, the ability of PPARα to bind to PPRE and the expression levels of PPARα, were both upregulated by AQP7 overexpression, as was the expression of a series of genes targeted by PPARα. Furthermore, downregulating HIF-1β and HIF-2α could elevate the expression levels of AQP7 and PPARα in ccRCC. Conclusions: AQP7 is suppressed in ccRCC and AQP7 may be a promising prognostic marker for the disease. Suppression of AQP7 in ccRCC contributes to lipid metabolism and cell cycle acceleration. The HIF/AQP7/PPARα axis might be an avenue for ccRCC treatment targeting lipid metabolism.

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Section: Discussionmentioning

confidence: 99%

Suppression of AQP7 is Crucial for Proliferation and Lipid Metabolism in ccRCC

Zhao,

Wang,

Jin

et al. 2024

Preprint

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“…In another study, a TLR3 ligand notably increased breast cancer cell proliferation, as indicated by the upregulation of cyclin D1 expression. However, the introduction of a MyD88 inhibitor disrupted the signal transduction of the TLR3-MyD88-NF-kB (p65)-IL6-Cyclin D1 pathway, leading to reduced breast cancer cell proliferation (37). Holleman et al also confirmed that reduced MyD88 expression significantly inhibited MCF-7 cell proliferation (38).…”

Section: Effect Of Myd88 On Breast Cancer Proliferationmentioning

confidence: 99%

MyD88 signaling pathways: role in breast cancer

Zheng,

Wu,

Guo

et al. 2024

Front. Oncol.

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MyD88 plays a central role in breast cancer, exerting a multitude of effects that carry substantial implications. Elevated MyD88 expression is closely associated with aggressive tumor characteristics, suggesting its potential as a valuable prognostic marker and therapeutic target. MyD88 exerts influence over several critical aspects of breast cancer, including metastasis, recurrence, drug resistance, and the regulation of cancer stem cell properties. Furthermore, MyD88 modulates the release of inflammatory and chemotactic factors, thereby shaping the tumor’s immune microenvironment. Its role in immune response modulation underscores its potential in influencing the dynamic interplay between tumors and the immune system. MyD88 primarily exerts intricate effects on tumor progression through pathways such as Phosphoinositide 3-kinases/Protein kinase B (PI3K/Akt), Toll-like Receptor/Nuclear Factor Kappa B (TLR/NF-κB), and others. Nevertheless, in-depth research is essential to unveil the precise mechanisms underlying the diverse roles of MyD88 in breast cancer. The translation of these findings into clinical applications holds great promise for advancing precision medicine approaches for breast cancer patients, ultimately enhancing prognosis and enabling the development of more effective therapeutic strategies.

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“…This culminates in cancer cellular proliferation. Inhibition of MyD88 can suppress the production of IL-6 and cyclinD1 and restrict cancer cell proliferation [50]. Another study suggested that breast cancer cells that transformed to a cancer stem cell phenotype possessed activated TLR3.…”

Section: Tlrs Activation In Immune Response and Inflammationmentioning

confidence: 99%

Multiple Factors Determine the Oncolytic or Carcinogenic Effects of TLRs Activation in Cancer

Yang,

Jin,

Yeo

et al. 2024

Journal of Immunology Research

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Toll-like receptors (TLRs) belong to a germline-encoded protein family. These are pattern recognition receptors. They sense pathogen-associated molecular patterns (PAMPs). When this occurs, activation of the NF-ĸB pathway follows. This triggers the innate immune response of the host. The consequent inflammatory cytokine response usually contributes to the elimination of the pathogen. Activation of TLRs also induces an adaptive immune response by a cross-prime mechanism. This mechanism is employed in cancer immunotherapy. Using TLR ligands as adjuvants induces upregulation of costimulatory signals which in turn activates a cytotoxic leukocyte response against cancer cells. However, TLRs are also overexpressed in human cancer cells resulting in increased cell proliferation, migration, invasion, and angiogenesis. An intracellular adaptor, myeloid differentiation factor 88 (MyD88) probably mediates this process. MyD88 is intimately involved with all TLRs except TLR3. One consequence of the interaction between a TLR and MyD88 is activation of NF-ĸB. In this context of a variety of proinflammtory cytokines being produced, chronic inflammation may result. Inflammation is an important protective mechanism. However, chronic inflammation is also involved in carcinogenesis. Activation of NF-ĸB inhibits apoptosis and under certain circumstances, tumor cell survival. In this review, the potential therapeutic value of TLRs in immunotherapy and its role in oncogenesis are explored. The emerging use of artificial intelligence is mentioned.

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Myeloid Differentiation Primary Response 88–Cyclin D1 Signaling in Breast Cancer Cells Regulates Toll-Like Receptor 3-Mediated Cell Proliferation

Cited by 5 publications

References 52 publications

Suppression of AQP7 is Crucial for Proliferation and Lipid Metabolism in ccRCC

Suppression of AQP7 is Crucial for Proliferation and Lipid Metabolism in ccRCC

MyD88 signaling pathways: role in breast cancer

Multiple Factors Determine the Oncolytic or Carcinogenic Effects of TLRs Activation in Cancer

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