Regulation of pro-angiogenic tissue factor expression in hypoxia-induced human lung cancer cells

Eisenreich, Andreas; Zakrzewicz, Andreas; Huber, Kilian; Thierbach, Hannes; Pepke, Wojciech; Goldin-Lang, Petra; Schultheiss, Heinz‐Peter; Pries, Axel R.; Rauch, Ursula

doi:10.3892/or.2013.2413

Cited by 41 publications

(103 citation statements)

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“…The authors suggested that SR protein-mediated control of asTF and flTF generation could potentially affect cancer-related thrombogenicity and angiogenesis (20 ). Recently, we demonstrated hypoxia to induce asTF and flTF expression in A549 lung cancer cells (2 ). In this context, we found the SR protein kinases cdc2-like kinase (Clk)1 and 4 to be involved in posttranscriptional regulation of hypoxia-induced TF isoform expression in A549 cells (2 ).…”

Section: Tf Isoform Expression In Cancermentioning

confidence: 85%

“…Recently, we demonstrated hypoxia to induce asTF and flTF expression in A549 lung cancer cells (2 ). In this context, we found the SR protein kinases cdc2-like kinase (Clk)1 and 4 to be involved in posttranscriptional regulation of hypoxia-induced TF isoform expression in A549 cells (2 ). MicroRNAs (miRNAs) are also involved in posttranscriptional expression control of TF and its isoforms.…”

Section: Tf Isoform Expression In Cancermentioning

confidence: 97%

“…Several factors are involved in enhanced TF expression in tumor tissues, such as hypoxia or genetic modifications of oncogenes and tumor suppressor genes, e.g. tumor protein p53 (TP53) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (2,4,17 ). These stimuli and events were shown to induce the transcription of the TF gene F3.…”

Section: Tf Isoform Expression In Cancermentioning

confidence: 99%

“…Because of alternative splicing TF is expressed in 3 mRNA splice variants: full-length (fl)TF, alternatively spliced (as)TF, and a third variant named TF-A. Translation of flTF and asTF mRNA splice variants leads to the generation of the flTF isoform, a membrane-bound and highly procoagulant protein (8 ), and soluble asTF with low prothrombogenic potential but strong proangiogenic, cell proliferationfacilitating, and prosurvival activities (2,9,10 ). The TF-A mRNA splice variant is not translated to a protein ( Fig.…”

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confidence: 99%

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Tissue Factor: A Conventional or Alternative Target in Cancer Therapy

2016

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BACKGROUND:Tissue factor (TF) is an evolutionary conserved glycoprotein that plays an important role in the pathogenesis of cancer. TF is expressed in 2 naturally occurring protein isoforms, membrane-bound full-length (fl)TF and soluble alternatively spliced (as)TF. Both isoforms have been shown to affect a variety of pathophysiologically relevant functions, such as tumor-associated angiogenesis, thrombogenicity, tumor growth, and metastasis. Therefore, targeting TF either by direct inhibition or indirectly, i.e., on a posttranscriptional level, offers a novel therapeutic option for cancer treatment.CONTENT: In this review we summarize the latest findings regarding the role of TF and its isoforms in cancer biology. Moreover, we briefly depict and discuss the therapeutic potential of direct and/or indirect inhibition of TF activity and expression for the treatment of cancer.

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Section: Tf Isoform Expression In Cancermentioning

confidence: 85%

Section: Tf Isoform Expression In Cancermentioning

confidence: 97%

Section: Tf Isoform Expression In Cancermentioning

confidence: 99%

mentioning

confidence: 99%

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Tissue Factor: A Conventional or Alternative Target in Cancer Therapy

2016

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“…In cancer cells, such as glioma, lung cancer, and breast cancer hypoxia induces TF [15,16,17]. On the other hand, the expression of TF in podocytes under hypoxic conditions is not known.…”

Section: Introductionmentioning

confidence: 99%

NF-κB-dependent increase in tissue factor expression is responsible for hypoxic podocyte injury

et al. 2015

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The role of tissue factor isoforms in cancer biology

Leppert

Eisenreich

2014

Int. J. Cancer

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Tissue Factor (TF) is an evolutionary conserved glycoprotein, which is of immense importance for a variety of biologic processes. TF is expressed in two naturally occurring protein isoforms, membrane-bound "full-length" (fl)TF and soluble alternatively spliced (as)TF. The TF isoform expression is differentially modulated on post-transcriptional level via regulatory factors, such as serine/arginine-rich (SR) proteins, SR protein kinases and micro (mi)RNAs. Both isoforms mediate a variety of physiologic-and pathophysiologic-relevant functions, such as thrombogenicity, angiogenesis, cell signaling, tumor cell proliferation and metastasis. In this review, we will depict the main mechanisms regulating the TF isoform expression in cancer and under other pathophysiologic-relevant conditions. Moreover, we will summarize and discuss the latest findings regarding the role of TF and its isoforms in cancer biology.Tissue factor (TF) is a glycoprotein and an evolutionary conserved member of the Class II cytokine receptor family, which was found in different species, such as human, mouse, rat, fish as well as in Drosophila melanogaster and mosquitos. 1-3 TF is expressed in two natural occurring protein isoforms, full-length (fl)TF and alternatively spliced (as)TF. [4][5][6] In human, flTF consists of a short intracellular domain (21 amino acids), a transmembrane domain (23 amino acids) and an extracellular domain (219 amino acids). 7 flTF is anchored to the cell membrane. 7,8 The primary function of flTF is the initiation of the blood coagulation cascade. 2,7,8 Beside this, flTF plays an important role in a variety of other biological processes, such as protease-activated receptor (PAR-)2-mediated cell signaling and tumor progression. 2,9,10 Due to alternative splicing the fifth exon of the primary TF transcript is excluded. 5,7 Translation of this messenger (m)RNA splice variant leads to the generation of asTF on protein level. asTF lacks the transmembrane domain and is therefore soluble. 7 Compared with flTF, asTF exhibits low prothrombogenic potential. 4,7,8 However, this isoform was recently linked more closely to angiogenesis, survival and cell growth. 3,[11][12][13][14] Post-transcriptional expression control regulate a variety of biologic functions, such as tumor cell invasion, metastasis and angiogenesis in cancer as well as in other settings. [15][16][17][18] Two major mechanisms modulate post-transcriptional expression: micro (mi)RNAs and alternative splicing processes. 16 In this review, we will discuss the latest findings regarding the impact of TF and its isoforms on cancer biology with special focus on pathophysiologic-relevant functions, such as thrombogenicity, tumor cell growth and angiogenesis. Moreover, we will shed light on the mechanisms regulating the TF isoform expression in cancer and under other pathophysiologic-relevant conditions. Cancer-Related Stimulation of TF ExpressionSeveral stimuli, such as hypoxia, vascular endothelial growth factor (VEGF) and the proinflammatory cytokine tumor necrosis fact...

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Regulation of pro-angiogenic tissue factor expression in hypoxia-induced human lung cancer cells

Cited by 41 publications

References 36 publications

Tissue Factor: A Conventional or Alternative Target in Cancer Therapy

Tissue Factor: A Conventional or Alternative Target in Cancer Therapy

NF-κB-dependent increase in tissue factor expression is responsible for hypoxic podocyte injury

The role of tissue factor isoforms in cancer biology

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