Biphasic Regulation of Mitogen-Activated Protein Kinase Phosphatase 3 in Hypoxic Colon Cancer Cells

Kim, Hong Seok; Kang, Yun Hee; Lee, Jisu; Han, Seung Ro; Kim, Da Bin; Ko, Haeun; Park, Seyoun; Lee, Myung‐Shin

doi:10.14348/molcells.2021.0093

Cited by 3 publications

(3 citation statements)

References 53 publications

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“…The results of the present study further revealed that DYRK1A-mediated HIF-1α expression could promote liver cancer chemoresistance in a hypoxic tumor microenvironment. Although DYRK1A regulated the expression of HIF-1α, HIF-1α still could be regulated by traditional signal pathway under hypoxia, such as PI3K and MAPK ( 25 , 26 ). Lee et al ( 13 ) and the present study demonstrated that DYRK1A is inhibited by hypoxia; it was hypothesized that it may act as a feedback loop when HIF-1α is activated by PI3K or MAPK pathway under hypoxia in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

DYRK1A suppression attenuates HIF‑1α accumulation and enhances the anti‑liver cancer effects of regorafenib and sorafenib under hypoxic conditions

Zhang

et al. 2022

Int J Oncol

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Hypoxia promotes drug resistance and induces the expression of hypoxia inducible factor (HIF)-1α in liver cancer cells. However, to date, no selective HIF-1α inhibitor has been clinically approved. The aim of this study is to investigate a drug-targetable molecule that can regulate HIF-1α under hypoxia. The present study demonstrated that hyperactivation of dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A)/HIF-1α signaling was associated with an increased risk of liver cancer. In addition, DYRK1A knockdown using small interfering RNA transfection or treatment with harmine, a natural alkaloid, significantly reduced the protein expression levels of HIF-1α in liver cancer cells under hypoxic conditions in vitro. Conversely, DYRK1A overexpression-vector transfection in liver cancer cell lines notably induced HIF-1α expression under the same conditions. Furthermore, DYRK1A was shown to interact and activate STAT3 under hypoxia to regulate HIF-1α expression. These findings indicated that DYRK1A may be a potential upstream activator of HIF-1α and positively regulate HIF-1α via the STAT3 signaling pathway in liver cancer cells. Additionally, treatment with harmine attenuated the proliferative ability of liver cancer cells under hypoxic conditions using sulforhodamine B and colony formation assay. Furthermore, DYRK1A knockdown could significantly enhance the anti-liver cancer effects of regorafenib and sorafenib under hypoxia. Co-treatment with harmine and either regorafenib or sorafenib also promoted cell death via the STAT3/HIF-1α/AKT signaling pathway under hypoxia using PI staining and western blotting. Overall, the results from the present study suggested that DYRK1A/HIF-1α signaling may be considered a novel pathway involved in chemoresistance, thus providing a potentially effective therapeutic regimen for treating liver cancer.

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Section: Discussionmentioning

confidence: 99%

DYRK1A suppression attenuates HIF‑1α accumulation and enhances the anti‑liver cancer effects of regorafenib and sorafenib under hypoxic conditions

Zhang

et al. 2022

Int J Oncol

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“…Mitogen-activated protein kinase phosphatase-3 (MKP-3) is a cytoplasmic dual-specificity phosphatase that preferentially dephosphorylates ERK (Muda et al 1996 ), which is a major trigger for the development of most types of cancers (Garcia-Gomez et al 2018 ; Maik-Rachline et al 2019 ). MKP-3 exerts a tumor-suppressive effect via the negative regulation of ERK in different types of cancers, including pancreatic (Furukawa et al 2003 ), lung (Okudela et al 2009 ), ovarian (Chan et al 2008 ), colon (Kim HS et al 2021 ), breast cancer (Luo et al 2015 ), and melanoma (Warmka et al 2004 ).…”

Section: Introductionmentioning

confidence: 99%

Scoparone attenuates PD-L1 expression in human breast cancer cells by MKP-3 upregulation

Kim,

Kim

2024

Animal Cells and Systems

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Breast cancer is a frequently occurring malignant tumor that is one of the leading causes of cancer-related deaths in women worldwide. Monoclonal antibodies that block programed cell death 1 (PD-1)/programed cell death ligand 1 (PD-L1) – a typical immune checkpoint – are currently the recommended standard therapies for many advanced and metastatic tumors such as triple-negative breast cancer. However, some patients develop drug resistance, leading to unfavorable treatment outcomes. Therefore, other approaches are required for anticancer treatments, such as downregulation of PD-L1 expression and promotion of degradation of PD-L1. Scoparone (SCO) is a bioactive compound isolated from Artemisia capillaris that exhibits antitumor activity. However, the effect of SCO on PD-L1 expression in cancer has not been confirmed yet. This study aimed to evaluate the role of SCO in PD-L1 expression in breast cancer cells in vitro. Our results show that SCO downregulated PD-L1 expression in a dose-dependent manner, via AKT inhibition. Interestingly, SCO treatment did not alter PTEN expression, but increased the expression of mitogen-activated protein kinase phosphatase-3 (MKP-3). In addition, the SCO-induced decrease in PD-L1 expression was reversed by siRNA-mediated MKP-3 knockdown. Collectively, these findings suggest that SCO inhibited the expression of PD-L1 in breast cancer cells by upregulating MKP-3 expression. Therefore, SCO may serve as an innovative combinatorial agent for cancer immunotherapy.

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“…During cell response to hypoxia, hypoxia‐inducible factor 1 (HIF‐1) is highly expressed, which is positively and significantly correlated with the progression of various cancers. [ 29,30 ] For instance, HIF‐1 α regulates tumor progression by influencing apoptotic/proliferative activity, vasomotor function, energy metabolism, and angiogenesis. Moreover, HIF‐1 α has been demonstrated to resist ROS in tumor cells, which may be a cellular self‐defense mechanism.…”

Section: Introductionmentioning

confidence: 99%

Engineered Red Blood Cell Membrane‐Coating Salidroside/Indocyanine Green Nanovesicles for High‐Efficiency Hypoxic Targeting Phototherapy of Triple‐Negative Breast Cancer

Pan

Zhao

et al. 2022

Adv Healthcare Materials

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Triple‐negative breast cancer (TNBC) presents special biological behavior and clinicopathological characteristics and leads to a worse prognosis than other types of breast cancer. The development of an effective therapeutic method is significant to improve the survival rate of TNBC cancer patients. In this work, an engineered red blood cell membrane (RBCm)‐coating salidroside/indocyanine green nanovesicle (ARISP) is successfully prepared for hypoxic targeting phototherapy of TNBC. Salidroside in ARISP effectively ameliorates hypoxia‐induced tumorigenesis by downregulating the expression of hypoxia‐inducible factor 1α (HIF‐1α), which increases the killing effect of reactive oxygen species on tumor cells during photodynamic therapy (PDT) using the photosensitizer indocyanine green. Besides, ARISP has an anti‐LDLR modified RBCm‐coating that extends its circulation time in the blood and escapes from immune surveillance and enhances hypoxia‐targeted cellular uptake via the overexpressed LDLR receptor in hypoxic tumor sites. Moreover, guided by near‐infrared fluorescence imaging and photoacoustic imaging, ARISP can eliminate tumors via high‐efficiency phototherapy and inhibit lung and liver metastasis in TNBC models. Cytotoxicity assay of ARISP indicates the excellent biocompatibility with normal cells and tissues. This study provides fulfilling insights into the anticancer mechanism of reducing HIF‐1α for enhanced PDT and has a promising therapeutic potential for TNBC treatment.

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Biphasic Regulation of Mitogen-Activated Protein Kinase Phosphatase 3 in Hypoxic Colon Cancer Cells

Cited by 3 publications

References 53 publications

DYRK1A suppression attenuates HIF‑1α accumulation and enhances the anti‑liver cancer effects of regorafenib and sorafenib under hypoxic conditions

DYRK1A suppression attenuates HIF‑1α accumulation and enhances the anti‑liver cancer effects of regorafenib and sorafenib under hypoxic conditions

Scoparone attenuates PD-L1 expression in human breast cancer cells by MKP-3 upregulation

Engineered Red Blood Cell Membrane‐Coating Salidroside/Indocyanine Green Nanovesicles for High‐Efficiency Hypoxic Targeting Phototherapy of Triple‐Negative Breast Cancer

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