Protein kinase Cδ in tumorigenesis of human malignant fibrous histiocytoma

Fukase, Naomasa; Kawamoto, Teruya; Kishimoto, Kenji; Hara, Hitomi; Okada, Yoshiyuki; Onishi, Yasuo; Toda, Mitsunori; Kurosaka, Masahiro; Akisue, Toshihiro

doi:10.3892/or.2011.1415

Cited by 5 publications

(6 citation statements)

References 34 publications

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“…Recently, we reported that Sp1 and PKC regulate the transcriptional expression of TMBIM6 8 . PKC was also highly expressed in various cancer types, as shown in liver, prostate, and breast cancers 10 , 11 . Although many pieces of evidence supported the involvement of TMBIM6 in the development of various cancers, the molecular mechanism underlying the role of TMBIM6 in cancer progression has been less studied.…”

Section: Introductionmentioning

confidence: 94%

TMBIM6/BI-1 contributes to cancer progression through assembly with mTORC2 and AKT activation

et al. 2020

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Transmembrane B cell lymphoma 2-associated X protein inhibitor motif-containing (TMBIM) 6, a Ca 2+ channel-like protein, is highly up-regulated in several cancer types. Here, we show that TMBIM6 is closely associated with survival in patients with cervical, breast, lung, and prostate cancer. TMBIM6 deletion or knockdown suppresses primary tumor growth. Further, mTORC2 activation is up-regulated by TMBIM6 and stimulates glycolysis, protein synthesis, and the expression of lipid synthesis genes and glycosylated proteins. Moreover, ER-leaky Ca 2+ from TMBIM6, a unique characteristic, is shown to affect mTORC2 assembly and its association with ribosomes. In addition, we identify that the BIA compound, a poten-tialTMBIM6 antagonist, prevents TMBIM6 binding to mTORC2, decreases mTORC2 activity, and also regulates TMBIM6-leaky Ca 2+ , further suppressing tumor formation and progression in cancer xenograft models. This previously unknown signaling cascade in which mTORC2 activity is enhanced via the interaction with TMBIM6 provides potential therapeutic targets for various malignancies.

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Section: Introductionmentioning

confidence: 94%

TMBIM6/BI-1 contributes to cancer progression through assembly with mTORC2 and AKT activation

et al. 2020

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“…Likewise, PKCδ has been shown to function as a tumor promoter in most (but not all) mouse models of cancer studied (Mauro et al, 2010; Symonds et al, 2011; Allen-Petersen, Carter, Ohm, & Reyland, 2014). Changes in PKCδ expression have been reported in some human tumors (Kahl-Rainer, Karner-Hanusch, Weiss, & Marian, 1994; D’Costa et al, 2006; Reno et al, 2008; Fukase et al, 2011) and increased PKCδ expression correlates with poor prognosis in specific subtypes of human breast cancer (McKiernan et al, 2008; Allen-Petersen et al, 2014). Notably, functional genomic alterations of PKCδ are rarely found (Antal & Newton, 2014).…”

Section: Biological Functions Of Pkcδmentioning

confidence: 99%

“…Similarly, Mischak et al showed that overexpression of PKCδ could suppress proliferation of NIH 3T3 cells (Mischak et al, 1993), and similar findings have been reported in a variety of cancer cells. For instance, PKCδ negatively regulates the Wnt pathway to suppress proliferation of colon cancer cells (Hernández-Maqueda, Luna-Ulloa, Santoyo-Ramos, Castañeda-Patlán, & Robles-Flores, 2013), Gli1 activation and Hedgehog signaling in hepatocellular carcinoma(Cai, Li, Gao, Xie, & Evers, 2009), ERK activation in breast cancer cells, and the proliferation and migration of human malignant fibrous histocytoma cells (Fukase et al, 2011). PKCδ also regulates apoptosis in prostate cancer cells through a mechanismin dependent of caspase cleavage and that involves the p38MAPK pathway (Fujii et al, 2000; Tanaka, Gavrielides, Mitsuuchi, Fujii, & Kazanietz, 2003).…”

Section: Biological Functions Of Pkcδmentioning

confidence: 99%

Multifunctional roles of PKCδ: Opportunities for targeted therapy in human disease

Reyland

Jones

2016

Pharmacology & Therapeutics

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The serine–threonine protein kinase, protein kinase C-δ (PKCδ), is emerging as a bi-functional regulator of cell death and proliferation. Studies in PKCδ−/− mice have confirmed a pro-apoptotic role for this kinase in response to DNA damage and a tumor promoter role in some oncogenic contexts. In non-transformed cells, inhibition of PKCδ suppresses the release of cytochrome c and caspase activation, indicating a function upstream of apoptotic pathways. Data from PKCδ−/− mice demonstrate a role for PKCδ in the execution of DNA damage-induced and physiologic apoptosis. This has led to the important finding that inhibitors of PKCδ can be used therapeutically to reduce irradiation and chemotherapy-induced toxicity. By contrast, PKCδ is a tumor promoter in mouse models of mammary gland and lung cancer, and increased PKCδ expression is a negative prognostic indicator in Her2+ and other subtypes of human breast cancer. Understanding how these distinct functions of PKCδ are regulated is critical for the design of therapeutics to target this pathway. This review will discuss what is currently known about biological roles of PKCδ and prospects for targeting PKCδ in human disease.

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“…This is exemplified by the use of prostate cancer cells as a model system to study distinct roles of PKC isozymes in apoptosis in prostate cancer cells [25], in which treatment of LNCaP, but not DU 145 and PC-3 cells, with PMA induces apoptosis [26]. Consistent with their differential roles in cell-based studies, the expression level of several PKC isozymes in some human cancers inversely correlates with the aggressiveness of the disease [27, 28]. However, the mechanism by which down-regulation of PKC isozymes regulates cancer cell growth remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional activation of PRMT5 by NF-Y is required for cell growth and negatively regulated by the PKC/c-Fos signaling in prostate cancer cells

Zhang

Zha

et al. 2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Protein arginine methyltransferase 5 (PRMT5) symmetrically methylates arginine residues of histones and non-histone protein substrates and regulates a variety of cellular processes through epigenetic control of target gene expression or post-translational modification of signaling molecules. Recent evidence suggests that PRMT5 may function as an oncogene and its overexpression contributes to the development and progression of several human cancers. However, the mechanism underlying the regulation of PRMT5 expression in cancer cells remains largely unknown. In the present study, we have mapped the proximal promoter of PRMT5 to the −240 bp region and identified nuclear transcription factor Y (NF-Y) as a critical transcription factor that binds to the two inverted CCAAT boxes and regulates PRMT5 expression in multiple cancer cell lines. Further, we present evidence that loss of PRMT5 is responsible for cell growth inhibition induced by knockdown of NF-YA, a subunit of NF-Y that forms a heterotrimeric complex with NF-YB and NF-YC for function. Significantly, we have found that activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) in LNCaP prostate cancer cells down-regulates the expression of NF-YA and PRMT5 at the transcription level in a c-Fos-dependent manner. Given that down-regulation of several PKC isozymes is implicated in the development and progression of several human cancers, our findings suggest that the PKC-c-Fos-NF-Y signaling pathway may be responsible for PRMT5 overexpression in a subset of human cancer patients.

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Protein kinase Cδ in tumorigenesis of human malignant fibrous histiocytoma

Cited by 5 publications

References 34 publications

TMBIM6/BI-1 contributes to cancer progression through assembly with mTORC2 and AKT activation

TMBIM6/BI-1 contributes to cancer progression through assembly with mTORC2 and AKT activation

Multifunctional roles of PKCδ: Opportunities for targeted therapy in human disease

Transcriptional activation of PRMT5 by NF-Y is required for cell growth and negatively regulated by the PKC/c-Fos signaling in prostate cancer cells

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