Enterobacteria impair host p53 tumor suppressor activity through mRNA destabilization

Aschtgen, Marie‐Stéphanie; Fragkoulis, Konstantinos; Sanz, Gema; Normark, Staffan; Selivanova, Galina; Henriques‐Normark, Birgitta; Peuget, Sylvain

doi:10.1038/s41388-022-02238-5

Cited by 6 publications

(5 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, some reports suggest that microbiota impair p53 tumor suppressor activity through mRNA instability in cancer pathophysiology. For example, some researchers have found that Enterobacteriaceae alleviate the selective pressure for p53 cancer-causing mutations and shape the genomic evolution of cancer through (Toll-like receptor 4) TLR4 repression of p53 [359]. In colorectal cancer, mut-p53 were found to have contrasting effects in different segments of the gut: in the distal gut, mut-p53 had the expected oncogenic effect; however, in the proximal gut and in tumor organoids, it had a pronounced tumor-suppressive effect [360].…”

Section: Microbiomementioning

confidence: 99%

Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy

Song,

Yang,

Zhang

2024

Cancer Communications

View full text Add to dashboard Cite

Cancer is a leading cause of death worldwide. Targeted therapies aimed at key oncogenic driver mutations in combination with chemotherapy and radiotherapy as well as immunotherapy have benefited cancer patients considerably. Tumor protein p53 (TP53), a crucial tumor suppressor gene encoding p53, regulates numerous downstream genes and cellular phenotypes in response to various stressors. The affected genes are involved in diverse processes, including cell cycle arrest, DNA repair, cellular senescence, metabolic homeostasis, apoptosis, and autophagy. However, accumulating recent studies have continued to reveal novel and unexpected functions of p53 in governing the fate of tumors, for example, functions in ferroptosis, immunity, the tumor microenvironment and microbiome metabolism. Among the possibilities, the evolutionary plasticity of p53 is the most controversial, partially due to the dizzying array of biological functions that have been attributed to different regulatory mechanisms of p53 signaling. Nearly 40 years after its discovery, this key tumor suppressor remains somewhat enigmatic. The intricate and diverse functions of p53 in regulating cell fate during cancer treatment are only the tip of the iceberg with respect to its equally complicated structural biology, which has been painstakingly revealed. Additionally, TP53 mutation is one of the most significant genetic alterations in cancer, contributing to rapid cancer cell growth and tumor progression. Here, we summarized recent advances that implicate altered p53 in modulating the response to various cancer therapies, including chemotherapy, radiotherapy, and immunotherapy. Furthermore, we also discussed potential strategies for targeting p53 as a therapeutic option for cancer.

show abstract

Section: Microbiomementioning

confidence: 99%

Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy

Song,

Yang,

Zhang

2024

Cancer Communications

View full text Add to dashboard Cite

show abstract

“…In a murine model, the co-maturation of DCs and NK cells stimulated by TLR agonists shows considerable potential as an effective trigger of anti-tumor immune responses, highlighting a promising approach for developing DC-based vaccines in CRC immunotherapy [ 96 ]. Additionally, certain cancer-associated bacteria, such as Klebsiella pneumoniae, produce toxins like LPS that inhibit the p53 pathway through TLR4/NF-κB-mediated destabilization of TP53 mRNA, shaping the genomic evolution of cancer [ 97 ]. TLR4 signaling on IECs is crucial for recruiting and activating macrophages, influencing the tumor microenvironment, and promoting dysplastic lesions in CRC [ 98 ].…”

Section: Tlr4 Pathway-related Biochemical Processesmentioning

confidence: 99%

The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment

Luo,

Zhang,

et al. 2024

Molecules

View full text Add to dashboard Cite

The toll-like receptor 4 (TLR4) signaling pathway constitutes an intricate network of protein interactions primarily involved in inflammation and cancer. This pathway triggers intracellular signaling cascades, modulating transcription factors that regulate gene expression related to immunity and malignancy. Previous studies showed that colon cancer patients with low TLR4 expression exhibit extended survival times and the TLR4 signaling pathway holds a significant role in CRC pathogenesis. In recent years, traditional Chinese medicines (TCMs) have garnered substantial attention as an alternative therapeutic modality for CRC, primarily due to their multifaceted composition and ability to target multiple pathways. Emerging evidence indicates that specific TCM products, such as andrographolide, rosmarinic acid, baicalin, etc., have the potential to impede CRC development through the TLR4 signaling pathway. Here, we review the role and biochemical processes of the TLR4 signaling pathway in CRC, and natural products from TCMs affecting the TLR4 pathway. This review sheds light on potential treatment strategies utilizing natural TLR4 inhibitors for CRC, which contributes to the advancement of research and accelerates their clinical integration into CRC treatment.

show abstract

“…Impairment of the fundamental cellular processes of the host leads to the initiation and progression of tumor. A single cancer cell might develop into tumors having multiple clones of tumor cells, therefore, each cancer cell might respond differently to anticancer therapies [94]. These variations in tumor cell populations are connected with the resistance to anticancer therapy [95].…”

Section: Burkholderia Bacteroides Fragilismentioning

confidence: 99%

Gut microbiome as a tumor promoter and tumor suppressor

Yadav,

Syal,

Tripathi

2023

Microsphere

View full text Add to dashboard Cite

The human microbiome is the aggregate of all the microbiota that reside on and within the human body. They have the ability to affect the homeostasis of the host body and change its pathology by the production of various metabolites. There is complex crosstalk occurring between the gut microbiome and the host through the gut-brain axis. Gut microbiome plays a dual role in cancer by promoting as well as by inhibiting tumor formation. Tumor formation may be initiated by the release of certain metabolites which cause degradation and DNA breaks. However, a number of probiotic microbiota, residing in the gut can help prevent cancer initiation by provoking apoptosis in cancer cells, as well as increasing the efficiency of anticancer therapy and reducing its toxicity outcomes. Any imbalance in the microbiome composition leads to the alteration of the non-pathogenic potential of the microbiome and an increased risk of diseases in the host. Establishing a robust understanding of this interplay can be instrumental for understanding the factors leading to tumor formation. This review highlights the interplay between the host and gut microbiome, as well as the role of the gut microbiome in cancer prevention, tumor formation, and anticancer therapy.

show abstract

Enterobacteria impair host p53 tumor suppressor activity through mRNA destabilization

Cited by 6 publications

References 76 publications

Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy

Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy

The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment

Gut microbiome as a tumor promoter and tumor suppressor

Contact Info

Product

Resources

About