Hes1 promotes cell proliferation and migration by activating Bmi-1 and PTEN/Akt/GSK3β pathway in human colon cancer

Gao, Fei; Huang, Wei; Zhang, Yuqin; Tang, Shaohui; Zheng, Lin; Ma, Feng; Wang, Yiming; Tang, Hui; Li, Xin

doi:10.18632/oncotarget.5484

Cited by 44 publications

(32 citation statements)

References 30 publications

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“…pAkt is activated in various types of OSCC and has been confirmed to promote cell proliferation, invasion, migration and reduce apoptosis (23,35). Research has shown that loss of PTEN function may be a factor leading to Akt signaling pathway activation and is consistent with the results of the present study (14,36). …”

Section: Discussionsupporting

confidence: 93%

Downregulation of miR-221/222 by a microRNA sponge promotes apoptosis in oral squamous cell carcinoma cells through upregulation of PTEN

et al. 2016

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MicroRNA-221 and microRNA-222 (miR-221/222) have been identified as oncogenes and confirmed to be overexpressed in various types of cancer. However, the regulation mechanism of miR-221/222 in oral squamous cell carcinoma (OSCC) remains to be fully elucidated. Previously, an miR-221/222 sponge was successfully constructed and its effect on the downregulation of miR-221/222 expression was investigated. In the present study, the dual luciferase reporter assay revealed a phosphatase and tensin homolog (PTEN) deletion on chromosome 10 to be a target gene of miR-221/222. It was also demonstrated that miR-221/222 suppression by transfection with an miR-221/222 sponge in vitro resulted in upregulation of PTEN. Notably, the proliferation and invasiveness of the miR-221/222 sponge-transfected cells was significantly inhibited, while apoptosis was promoted, when determined by Cell Counting Kit-8, Transwell assays and flow cytometry. The results of the present study prove that miR-221/222 may downregulate the expression of PTEN in OSCC cells and function as oncogenes, providing a novel insight into the underlying mechanism of OSCC tumorigenesis. The present study suggests that upregulating the expression of PTEN by downregulation of miR-221/222 may be a potential treatment for OSCC.

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Section: Discussionsupporting

confidence: 93%

Downregulation of miR-221/222 by a microRNA sponge promotes apoptosis in oral squamous cell carcinoma cells through upregulation of PTEN

et al. 2016

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“…Notably, HES1 has also been implicated in EMT-induced tumor invasion and metastasis, which facilitates the loss of cell adhesion and increases motility and survival in the detached condition (17,29). A previous study has suggested that HES1 facilitates EMT processes by activating the protein kinase B/ phosphatase and tensin homolog axis, which has critical effects on the regulation of EMT in tumors (17).…”

Section: Discussionmentioning

confidence: 99%

Lutein inhibits proliferation, invasion and migration of hypoxic breast cancer cells via downregulation of HES1

Zhang

Liu

et al. 2018

Int J Oncol

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An intratumoral hypoxic microenvironment is frequently observed in solid tumors, including breast cancer. Lutein, a plant-derived compound and non-vitamin A carotenoid, has been demonstrated to possess multiple protective properties including anti-inflammation, anti-oxidative stress and antitumor effects. The main objective of the present research was to elucidate the involvement of lutein in the production of reactive oxygen species (ROS) under hypoxia, the activation of hairy and enhancer of split 1 (HES1), and the proliferation, invasion and migration of breast cancer cells. The human breast cancer cell lines MDA‑MB‑157 and MCF‑7 were exposed to hypoxic conditions and various concentrations of lutein. An MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was performed to examine cell proliferation, and Annexin V-fluorescein isothiocyanate/propidium iodide staining was performed to analyze the apoptosis ratio. The levels of hypoxia inducible factor-1α (HIF‑1α), NOTCH signaling molecules, HES1 and epithelial-mesenchymal transition (EMT)-associated factors were examined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. Wound healing and Transwell invasion assays were used to detect the invasion and migration of breast cancer cells. Intracellular ROS levels were examined using 2,7-dichlorodihydrofluorescein-diacetate and flow cytometry. The results revealed that cell proliferation was inhibited by lutein in a dose-dependent manner, and the apoptosis ratio gradually increased with lutein treatment under hypoxia as evident from flow cytometry-based analysis. Exposure to lutein inhibited hypoxia-mediated activation of HIF‑1α, NOTCH signaling and HES1 expression, and suppressed the hypoxia-induced expression of EMT-associated factors. Lutein markedly inhibited the invasion and migration of breast cancer cells under hypoxia. Hypoxia-induced production of ROS was also decreased by lutein. Furthermore, the ROS scavenger N‑acetylcysteine also suppressed hypoxia inducible factor 1α and HES1 expression in breast cancer cells during hypoxia, but hydrogen peroxide (H2O2) levels were increased. Taken together, the results of the present study suggested that lutein may be a novel candidate for the chemoprevention of breast cancer. Furthermore, HES1 may be crucial in mediating the involvement of lutein in the suppression of hypoxia-driven ROS-induced breast cancer progression.

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“…S4C). Previous studies showed that Hes1 directly suppresses Pten (28,29), which upregulates p53 activity (30) and downregulates the PI3K-Akt pathway (31) to induce apoptosis. Interestingly, Pten was upregulated in the Hes1-deleted TSCs, but not in the Hes1-deleted NSCs at day 1 ( Fig.…”

Section: Hes1 Deletion In Lgr5 þ Tscs Of Established Intestinal Tumormentioning

confidence: 99%

Distinct Roles of HES1 in Normal Stem Cells and Tumor Stem-like Cells of the Intestine

et al. 2017

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Cancer stem cells (CSC) have attracted attention as therapeutic targets; however, CSC-targeting therapy may disrupt normal tissue homeostasis because many CSC molecules are also expressed by normal stem cells (NSC). Here, we demonstrate that NSC-specific and CSC-specific roles of the stem cell transcription factor Hes1 in the intestine enable the feasibility of a specific cancer therapy. Hes1 expression was upregulated in NSCs and intestinal tumors. Lineage-tracing experiments in adult mouse intestine revealed that Hes1 deletion in Lgr5 or Bmi1 NSCs resulted in loss of self-renewal but did not perturb homeostasis. Furthermore, in Lgr5 NSC, deletion of Hes1 and β-catenin stabilization limited tumor formation and prolonged host survival. Notably, in Lgr5 or Dclk1 tumor stem cells derived from established intestinal tumors, Hes1 deletion triggered immediate apoptosis, reducing tumor burden. Our results show how Hes1 plays different roles in NSCs and CSCs, in which Hes1 disruption leads to tumor regression without perturbing normal stem cell homeostasis, preclinically validating Hes1 as a cancer therapeutic target. .

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Hes1 promotes cell proliferation and migration by activating Bmi-1 and PTEN/Akt/GSK3β pathway in human colon cancer

Cited by 44 publications

References 30 publications

Downregulation of miR-221/222 by a microRNA sponge promotes apoptosis in oral squamous cell carcinoma cells through upregulation of PTEN

Downregulation of miR-221/222 by a microRNA sponge promotes apoptosis in oral squamous cell carcinoma cells through upregulation of PTEN

Lutein inhibits proliferation, invasion and migration of hypoxic breast cancer cells via downregulation of HES1

Distinct Roles of HES1 in Normal Stem Cells and Tumor Stem-like Cells of the Intestine

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