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Cdh1 functions as an oncogene by inducing self-renewal of lung cancer stem-like cells via oncogenic pathways.

ABSTRACT: The mortality rate of lung cancer remains the highest amongst all cancers despite of new therapeutic developments. While cancer stem cells (CSCs) may play a pivotal role in cancer, mechanisms underlying CSCs self-renewal and their relevance to cancer progression have not been clearly elucidated due to the lack of reliable and stable CSC cellular models. In the present study, we unveiled the novel oncogene function of cadherin 1 (Cdh1) via bioinformatic analysis in a broad spectrum of human cancers including lung adenocarcinoma (LUAD), adding a new dimension to the widely reported tumor suppressor function of Cdh1. Experimentally, we show for the first time that Cdh1 promotes the self-renewal of lung CSCs, consistent with its function in embryonic and normal stem cells. Using the LLC-Symmetric Division (LLC-SD) model, we have revealed an intricate cross-talk between the oncogenic pathway and stem cell pathway in which Cdh1 functions as an oncogene by promoting lung CSC renewal via the activation of the Phosphoinositide 3-kinase (PI3K) and inhibition of Mitogen-activated protein kinase (MAPK) pathways, respectively. In summary, this study has provided evidence demonstrating effective utilization of the normal stem cell renewal mechanisms by CSCs to promote oncogenesis and progression.

SUBMITTER: Ye T

PROVIDER: S-EPMC6990901 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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<i>Cdh1</i> functions as an oncogene by inducing self-renewal of lung cancer stem-like cells via oncogenic pathways.

Ye Ting T Li Jingyuan J Sun Zhiwei Z Liu Doudou D Zeng Bin B Zhao Qiting Q Wang Jianyu J Xing H Rosie HR

International journal of biological sciences 20200101 3

The mortality rate of lung cancer remains the highest amongst all cancers despite of new therapeutic developments. While cancer stem cells (CSCs) may play a pivotal role in cancer, mechanisms underlying CSCs self-renewal and their relevance to cancer progression have not been clearly elucidated due to the lack of reliable and stable CSC cellular models. In the present study, we unveiled the novel oncogene function of cadherin 1 (<i>Cdh1</i>) via bioinformatic analysis in a broad spectrum of huma ...[more]

PMID: 32015681

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Project description:Extensive cancer research in the past few decades has identified the existence of a rare subpopulation of stem cells in the grove of cancer cells. These cells are known as the cancer stem cells marked by the presence of surface biomarkers, multi-drug resistance pumps and deregulated self-renewal pathways (SRPs). They have a crucial role in provoking cancer cells leading to tumorigenesis and its progressive metastasis. Cancer stem cells (CSCs) are much alike to normal stem cells in their self-renewal mechanisms. However, deregulations in the SRPs are seen in CSCs, making them resistant to conventional chemotherapeutic agents resulting in the tumor recurrence. Current treatment strategies in cancer fail to detect and differentiate the CSCs from their non-tumorigenic progenies owing to absence of specific biomarkers. Now, it has become imperative to understand complex functional biology of CSCs, especially the signaling pathways to design improved treatment strategies to target them. It is hopeful that the SRPs in CSCs offer a promising target to alter their survival strategies and impede their tumorigenic potential. However, there are many perils associated with the direct targeting method by conventional therapeutic agents such as off targets, poor bioavailability and poor cellular distribution. Recent evidences have shown an increased use of small molecule antagonists directly to target these SRPs may lead to severe side-effects. An alternative to solve these issues could be an appropriate nanoformulation. Nanoformulations of these molecules could provide an added advantage for the selective targeting of the pathways especially Hedgehog, Wnt, Notch and B-cell-specific moloney murine leukemia virus integration site 1 in the CSCs while sparing the normal stem cells. Hence, to achieve this goal a complete understanding of the molecular pathways corroborate with the use of holistic nanosystem (nanomaterial inhibition molecule) could possibly be an encouraging direction for future cancer therapy.

Dataset Information

Cdh1 functions as an oncogene by inducing self-renewal of lung cancer stem-like cells via oncogenic pathways.

Publications

<i>Cdh1</i> functions as an oncogene by inducing self-renewal of lung cancer stem-like cells via oncogenic pathways.

Similar Datasets

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