Dataset Information

Beyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy.

ABSTRACT: Here, we provide an overview of the importance of cellular fate in cancer as a group of diseases of abnormal cell growth. Tumor development and progression is a highly dynamic process, with several phases of evolution. The existing evidence about the origin and consequences of cancer cell fate specification (e.g., proliferation, senescence, stemness, dormancy, quiescence, and cell cycle re-entry) in the context of tumor formation and metastasis is discussed. The interplay between these dynamic tumor cell phenotypes, the microenvironment, and the immune system is also reviewed in relation to cancer. We focus on the role of senescence during cancer progression, with a special emphasis on its relationship with stemness and dormancy. Selective interventions on senescence and dormancy cell fates, including the specific targeting of cancer cell populations to prevent detrimental effects in aging and disease, are also reviewed. A new conceptual framework about the impact of synthetic lethal strategies by using senogenics and then senolytics is given, with the promise of future directions on innovative anticancer therapies.

SUBMITTER: Triana-Martinez F

PROVIDER: S-EPMC7072600 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Beyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy.

Triana-Martínez Francisco F Loza María Isabel MI Domínguez Eduardo E

Cells 20200203 2

Here, we provide an overview of the importance of cellular fate in cancer as a group of diseases of abnormal cell growth. Tumor development and progression is a highly dynamic process, with several phases of evolution. The existing evidence about the origin and consequences of cancer cell fate specification (e.g., proliferation, senescence, stemness, dormancy, quiescence, and cell cycle re-entry) in the context of tumor formation and metastasis is discussed. The interplay between these dynamic t ...[more]

PMID: 32028565

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Project description:Hyperactivation of the Wingless-type (Wnt)/β-catenin pathway promotes tumor initiation, tumor growth and metastasis in various tissues. Although there is evidence for the involvement of Wnt/β-catenin pathway activation in salivary gland tumors, the precise mechanisms are unknown. Here we report for the first time that downregulation of the Wnt inhibitory factor 1 (WIF1) is a widespread event in salivary gland carcinoma ex-pleomorphic adenoma (CaExPA). We also show that WIF1 downregulation occurs in the CaExPA precursor lesion pleomorphic adenoma (PA) and indicates a higher risk of progression from benign to malignant tumor. Our results demonstrate that diverse mechanisms including WIF1 promoter hypermethylation and loss of heterozygosity contribute to WIF1 downregulation in human salivary gland tumors. In accordance with a crucial role in suppressing salivary gland tumor progression, WIF1 re-expression in salivary gland tumor cells inhibited cell proliferation, induced more differentiated phenotype and promoted cellular senescence, possibly through upregulation of tumor-suppressor genes, such as p53 and p21. Most importantly, WIF1 significantly diminished the number of salivary gland cancer stem cells and the anchorage-independent cell growth. Consistent with this observation, WIF1 caused a reduction in the expression of pluripotency and stemness markers (OCT4 and c-MYC), as well as adult stem cell self-renewal and multi-lineage differentiation markers, such as WNT3A, TCF4, c-KIT and MYB. Furthermore, WIF1 significantly increased the expression of microRNAs pri-let-7a and pri-miR-200c, negative regulators of stemness and cancer progression. In addition, we show that WIF1 functions as a positive regulator of miR-200c, leading to downregulation of BMI1, ZEB1 and ZEB2, with a consequent increase in downstream targets such as E-cadherin. Our study emphasizes the prognostic and therapeutic potential of WIF1 in human salivary gland CaExPA. Moreover, our findings demonstrate a novel mechanism by which WIF1 regulates cancer stemness and senescence, which might have major implications in the field of cancer biology.

Dataset Information

Beyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy.

Publications

Beyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy.

Similar Datasets

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