Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell–Cell Adhesion and Invasive Cell Migration in Human Breast Cancer

Tokuda, Emi; Itoh, Toshiki; Hasegawa, Junya; Ijuin, Takeshi; Takeuchi, Kosei; Irino, Yasuhiro; Fukumoto, Manabu; Takenawa, Tadaomi

doi:10.1158/0008-5472.can-13-2441

Cited by 62 publications

(95 citation statements)

References 42 publications

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“…Golgi protein GOLM1 is related to the development of prostate cancer [11]. Phosphatidylinositol 4-phosphate can regulate the adhesion of tumor cells thus influence the metastasis of breast cancer [12], and it is reported that the polarization of the Golgi body also participates in the metastasis of breast cancer [13]. In addition, the Golgi apparatus also participate in colorectal cancer by controlling the sensitivity of mTOR to amino acids, and is closely related to the prognosis of colorectal cancer [14].…”

Section: Discussionmentioning

confidence: 99%

Golgi integral membrane protein 4 manipulates cellular proliferation, apoptosis, and cell cycle in human head and neck cancer

et al. 2018

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The incidence of global head and neck cancer has increased markedly in the last 10 years, and its prognosis is poor, which seriously endangers people’s life and health. At present, there are few studies on its pathogenesis. Golgi integral membrane protein 4 (GOLIM4) is a major member of the Golgi apparatus transporter complex, and its role in tumor is unclear. The present study found that GOLIM4 was the key target protein downstream of stromal interaction molecule 1 (STIM1), which can inhibit the proliferation of head and neck cancer cells FaDu (human pharyngeal squamous carcinoma cell) and Tca-8113 (human tongue squamous carcinoma cell) with knockdown of GOLIM4 by lentivirus. And the decreased expression of GOLIM4 induced cellular apoptosis. Further experiments revealed that FaDu cell cycle progression was changed after GOLIM4 silence, G1 phase arrest and the number of G2/M cells decreased significantly. It was also found that the cells in S-phase decreased markedly after GOLIM4 was knocked down compared with the control group by 5-bromo-2′-deoxyuridine (BrdU) incorporation experiment. In conclusion, we found that GOLIM4, as the target gene downstream of STIM1, inhibited the proliferation of head and neck cancer, promoted apoptosis, and regulated cell cycle progression, and GOLIM4 is a novel oncogene in head and neck cancer and might help in developing promising targetted therapies for head and neck cancer patients.

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Section: Discussionmentioning

confidence: 99%

Golgi integral membrane protein 4 manipulates cellular proliferation, apoptosis, and cell cycle in human head and neck cancer

et al. 2018

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“…It is striking that reduced capacity of cellular adhesion is relevant for adaption of CHO cells to suspension culture, which is a CHO cell property necessary for scalability of industrial processes. It is also strongly related to the conversion of benign tumors to aggressive cancers (Tokuda et al, 2014). Interestingly, PMDs in placenta tissue, SH-SY5Y and IMR90 cells are most significantly enriched in genes contributing to neurological processes, too .…”

Section: The Cho Dp-12 Cell Dna Methylome Shows Evidence Of Partiallymentioning

confidence: 99%

The DNA methylation landscape of Chinese hamster ovary (CHO) DP-12 cells

Wippermann

Rupp

Brinkrolf

et al. 2015

Journal of Biotechnology

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Chinese hamster ovary (CHO) cells represent the most commonly used production cell line for therapeutic proteins. By recent genome and transcriptome sequencing a basis was created for future investigations of genotype-phenotype relationships and for improvement of CHO cell productivity and product quality. In this context information is missing about DNA cytosine methylation as a crucial epigenetic modification and an important element in mammalian genome regulation and development. Here, we present the first DNA methylation map of a CHO cell line in single-base resolution that was generated by whole genome bisulfite sequencing combined with gene expression analysis by CHO microarrays. We show CHO DP-12 cells to exhibit global hypomethylation compared to a majority of mammalian methylomes and hypermethylation of CpG-dense regions at gene promoters called CpG islands. We also observed partially methylated domains that cover 62% of the CHO DP-12 cell genome and contain functional clusters of genes. Gene expression analysis showed these clusters to be either highly or weakly expressed with regard to CHO-specific characteristics and hence proves DNA methylation in CHO cells to be an important link between genomics and transcriptomics.

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“…PI4KIIa knockout mice develop late-onset neurologic features that resemble human hereditary spastic paraplegia (15). Recently, an increasing number of reports have identified PI4KIIa as a potential target for breast cancer therapy (3,4,(16)(17)(18)(19). We previously reported that increased PI4KIIa expression promotes tumor growth by altering the HER2/PI3-kinase (PI3K)/ERK signaling cascades (4) and that dual inhibition of EGFR and PI4KIIa represents a novel strategy to combat EGFR-dependent tumors (17).…”

Section: Introductionmentioning

confidence: 99%

PI-273, a Substrate-Competitive, Specific Small-Molecule Inhibitor of PI4KIIα, Inhibits the Growth of Breast Cancer Cells

Gao

Zhao

et al. 2017

Cancer Research

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While phosphatidylinositol 4-kinase (PI4KIIa) has been identified as a potential target for antitumor therapy, the clinical applications of PI4KIIa are limited by a lack of specific inhibitors. Here we report the first small-molecule inhibitor (SMI) of human PI4KIIa. Docking-based and ligand-based virtual screening strategies were first employed to identify promising hits, followed by two rounds of kinase activity inhibition validation. 2-(3-(4-Chlorobenzoyl)thioureido)-4-ethyl-5-methylthiophene-3-carboxamide (PI-273) exhibited the greatest inhibitory effect on PI4KIIa kinase activity (IC 50 ¼ 0.47 mmol/L) and suppressed cell proliferation. Surface plasmon resonance and thermal shift assays indicated that PI-273 interacted directly with PI4KIIa. Kinetic analysis identified PI-273 as a reversible competitive inhibitor with respect to the substrate phosphatidylinositol (PI), which contrasted with most other PI kinase inhibitors that bind the ATP binding site. PI-273 reduced PI4P content, cell viability, and AKT signaling in wild-type MCF-7 cells, but not in PI4KIIa knockout MCF-7 cells, indicating that PI-273 is highly selective for PI4KIIa. Mutant analysis revealed a role of palmitoylation insertion in the selectivity of PI-273 for PI4KIIa. In addition, PI-273 treatment retarded cell proliferation by blocking cells in G 2 -M, inducing cell apoptosis and suppressing colony-forming ability. Importantly, PI-273 significantly inhibited MCF-7 cell-induced breast tumor growth without toxicity. PI-273 is the first substratecompetitive, subtype-specific inhibitor of PI4KIIa, the use of which will facilitate evaluations of PI4KIIa as a cancer therapeutic target. Cancer Res; 77(22); 6253-66. Ó2017 AACR.

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Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell–Cell Adhesion and Invasive Cell Migration in Human Breast Cancer

Cited by 62 publications

References 42 publications

Golgi integral membrane protein 4 manipulates cellular proliferation, apoptosis, and cell cycle in human head and neck cancer

Golgi integral membrane protein 4 manipulates cellular proliferation, apoptosis, and cell cycle in human head and neck cancer

The DNA methylation landscape of Chinese hamster ovary (CHO) DP-12 cells

PI-273, a Substrate-Competitive, Specific Small-Molecule Inhibitor of PI4KIIα, Inhibits the Growth of Breast Cancer Cells

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