The antagonism between MCT-1 and p53 affects the tumorigenic outcomes

Kasiappan, Ravi; Shih, Hung-Ju; Wu, Meng-Hsun; Choy, Chik-On; Lin, Tai-Du; Chen, Linyi; Hsu, Hsin-Ling

doi:10.1186/1476-4598-9-311

Cited by 17 publications

(27 citation statements)

References 60 publications

(71 reference statements)

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“…Based on pro‐inflammatory effects of macrophages and on cancer growth exerted by MIF which suppresses the function of p53 [Bifulco et al, ], one could reason that the MIF‐driven cancer cell proliferation, invasiveness, and metastasis in response to IR observed in our study were due to suppressed p53 activity. However, A549 cells contain wild‐type p53 while NCI‐H358 cells lack expression of p53 [Kasiappan et al, ; Osborne et al, ]. Similar results from the two cell lines in almost all of our experiments suggest that p53 was not associated with the results of the present study.…”

Section: Discussionsupporting

confidence: 79%

Dissociation of MIF‐rpS3 Complex and Sequential NF‐κB Activation Is Involved in IR‐Induced Metastatic Conversion of NSCLC

Youn

Son

Kim

et al. 2015

J of Cellular Biochemistry

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Frequent relapse and spreading of tumors during radiotherapy are principal obstacles to treatment of non-small cell lung cancer (NSCLC). In this study, we aimed to investigate how macrophage migration inhibitory factor (MIF) which is expressed at high levels in metastatic and primary lung cancer cells could regulate NSCLC metastasis in response to ionizing radiation (IR). The results indicated that MIF and ribosomal protein S3 (rpS3) were shown to be connected to inflammation, proliferation, and metastasis of NSCLC via IR-induced activation of the NF-κB pathway. Under unirradiated conditions, MIF physically established a complex with rpS3. MIF-rpS3 dissociation induced by IR activated NF-κB and made the expression of target genes of this factor transactivated in two NSCLC cell lines, A549, and NCI-H358. We also found that IR-induced dissociation of this complex led to increased secretion of pro-inflammatory cytokines and modulated the expression of epithelial-mesenchymal transition marker proteins. Finally, the effects of IR-induced dissociation of the MIF-rpS3 complex on tumor metastasis were confirmed by in vivo xenograft studies. Taken together, the present study revealed that dissociation of the MIF-rpS3 complex and subsequent activation of NF-κB is a critical post-IR exposure event that accounts for IR-induced metastatic conversion of NSCLC.

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Section: Discussionsupporting

confidence: 79%

Dissociation of MIF‐rpS3 Complex and Sequential NF‐κB Activation Is Involved in IR‐Induced Metastatic Conversion of NSCLC

Youn

Son

Kim

et al. 2015

J of Cellular Biochemistry

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“…Tumor samples were processed for immunohistochemical (IHC) staining as described previously [60]. Abs against VEGF Receptor 2 (1:800, D5B1, Cell signaling) and CD163 (1:100, ab182422, Abcam) were diluted in PBS as indicated.…”

Section: Tumor Growth In Xenograft Mice and A Tumor Immunohistochemismentioning

confidence: 99%

Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression

Chen

Tseng

Chen

et al. 2020

Cancers

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Reactive oxygen species (ROS) produced during intracellular metabolism or triggered by extrinsic factors can promote neoplastic transformation and malignant microenvironment that mediate tumor development. Oligo-Fucoidan is a sulfated polysaccharide isolated from the brown seaweed. Using human THP-1 monocytes and murine Raw264.7 macrophages as well as human HCT116 colorectal cancer cells, primary C6P2-L1 colorectal cancer cells and human MDA-MB231 breast cancer cells, we investigated the effect of Oligo-Fucoidan on inhibiting M2 macrophage differentiation and its therapeutic potential as a supplement in chemotherapy and tumor prevention. We now demonstrate that Oligo-Fucoidan is an antioxidant that suppresses intracellular ROS and mitochondrial superoxide levels in monocytes/macrophages and in aggressive cancer cells. Comparable to ROS inhibitors (DPI and NAC), Oligo-Fucoidan directly induced monocyte polarization toward M1-like macrophages and repolarized M2 macrophages into M1 phenotypes. DPI and Oligo-Fucoidan also cooperatively prevented M2 macrophage invasiveness. Indirectly, M1 polarity was advanced particularly when DPI suppressed ROS generation and supplemented with Oligo-Fucoidan in the cancer cells. Moreover, cisplatin chemoagent polarized monocytes and M0 macrophages toward M2-like phenotypes and Oligo-Fucoidan supplementation reduced these side effects. Furthermore, Oligo-Fucoidan promoted cytotoxicity of cisplatin and antagonized cisplatin effect on cancer cells to prevent M2 macrophage differentiation. More importantly, Oligo-Fucoidan inhibited tumor progression and M2 macrophage infiltration in tumor microenvironment, thus increasing of anti-tumor immunity.

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“…[37][38][39][40] In supporting MCT-1's tumorigenic role, overexpression of MCT-1 transforms normal breast epithelial cells and downregulates p53 expression at both gene and protein levels. 35,37,41 Moreover, MCT-1 oncogene promotes chromosome abnormalities in the p53-compromised cells upon genotoxic damage and enhances the xenograft tumorigenicity of H1299 (p53-null) lung cancer cells. 35 Though MCT-1 is phosphorylated by CDC2 and ERK kinase in vitro, 42 it is unknown whether MCT-1 is implicated in mitotic function.…”

Section: The Involvement Of Mct-1 Oncoprotein In Inducing Mitotic Catmentioning

confidence: 99%

The involvement of MCT-1 oncoprotein in inducing mitotic catastrophe and nuclear abnormalities

Shih

Chu

et al. 2012

Cell Cycle

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The antagonism between MCT-1 and p53 affects the tumorigenic outcomes

Cited by 17 publications

References 60 publications

Dissociation of MIF‐rpS3 Complex and Sequential NF‐κB Activation Is Involved in IR‐Induced Metastatic Conversion of NSCLC

Dissociation of MIF‐rpS3 Complex and Sequential NF‐κB Activation Is Involved in IR‐Induced Metastatic Conversion of NSCLC

Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression

The involvement of MCT-1 oncoprotein in inducing mitotic catastrophe and nuclear abnormalities

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