loading...| Preferred Name | Prostate Cancer | |
| Synonyms |
PathwayType: signaling PMID: 18667687 Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-a97ac062-8753-4ba3-afc5-3caa86b6ca97 CellType: cancer cell PMID: 17297502 PMID: 22417299 Notes: Headnote: Prostate cancer is a cancer that develops in the prostate gland. Prostate cancer cases are characterized by considerable heterogeneity especially during the progression to hormone-refractory status. This pathway describes the signaling cascades that could potentially exist in cancer cells, but may not necessarily occur in every case. Signaling description: It is generally accepted that androgen receptor (AR) plays a significant role in prostate cancer even upon transition to an androgen-independent state. This may be due to changes in either the receptor itself (e.g., mutations or amplifications) or in coregulators influencing AR activity (e.g., NCOA2, NCOA3, NCOA4, CCND1, and ARA55). However, in primary tumors AR activity is strongly dependent on androgens (testosterone and DHT) and antiandrogen therapy is used successfully to stop the progression of the cancer. Nevertheless, during this therapy the disease acquires androgen-refractory status characterized by deregulation of many signaling pathways. One of the deregulated signaling cascades in prostate cancer cells is the PI3K/Akt pathway that is found to be highly activated in advanced cases of the disease. The main cause of constitutive activation of Akt (AKT1) is the loss of PTEN function in advanced cancer since PI3K pathway inhibition is primarily performed by the tumor suppressor, PTEN. Another signaling cascade that is deregulated in prostate cancer is MAP kinase (MAPK) pathway. The main probable cause for permanent activation of the MAPK cascade in prostate cancer cells is increased levels of autocrine and paracrine growth factors. Additionally, prostate cancer cells are characterized by the overexpression of some growth factor receptors (e.g., ERBB2), that also activate growth factor pathways. Multiple growth factors and cytokines such as epidermal growth factor (EGF), insulin-like growth factor-1 (IGF1), and interleukin-6 (IL6) stimulate cell growth through the activation of small G-protein Ras and MAPK cascade. The phosphorylation of ERK1/2 (MAPK1/2) leads to the activation of various transcription factors such as MYC, ETS1, EGR1, SP1, and Jun/Fos and the modulation of downstream cell processes. In addition, the transmembrane receptor tyrosine kinase, c-Met (MET) plays an important role in prostate cancer. MET is activated by the hepatocyte growth factor/scatter factor (HGF/SF), which is a multifunctional growth factor that regulates various cell processes such as cell motility, invasive growth, and angiogenesis. AR inhibits the expression of MET by competing with another transcription factor, SP1 for binding to the promoter of MET gene. Lastly, there are several microRNAs (miRNAs) that play a major role in the pathogenesis and prognosis of prostate cancer. Several miRNAs and their targets have been discovered to express abnormally in some prostate cancer cases, including some that are oncogenic (MIR106B and MIR221) and tumor suppressive (MIR15A, MIR145, and MIR101-1). Outcome effects: AKT1 regulates cell survival and cell cycle. For example, AKT1 negatively regulates apoptosis by inhibiting procaspase-9 (CASP9) and BAD, while positively regulating the cell cycle by inhibiting p21 and p27, thus enabling cell cycle progression. Furthermore, AKT1 can also regulate AR activity. In the normal prostate, AR seems to balance proliferative and proapoptotic programs, while in cancerous tissue AKT1 can phosphorylate and inactivate AR, thereby permanently switching on a pro-survival program. Another target of AKT1 is enhancer of zeste homolog 2 (EZH2), which is a transcriptional repressor whose expression in prostate cancer is associated with hormone-refractory status and metastasis. Further, the MAPK pathway controls such processes as proliferation, metastasis, and angiogenesis as well as resistance to antitumor drugs. One of the transcriptional targets of MAPK signaling is interleukin-6 which can play a role in the progression of prostate cancer through sev Description: Prostate cancer cases are characterized by considerable heterogeneity especially during the progression to hormone-refractory status. Pathway is built manually using published studies. PMID: 21475371 Organ: prostate NodeType: Pathway PMID: 21956922 Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin PMID: 16741972 Organ_System: urinary tract Source: Diseases |
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| ID |
urn:agi-pathway:uuid-a97ac062-8753-4ba3-afc5-3caa86b6ca97 |
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| database_cross_reference |
PS:PathwayType PS:Description PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Organ PS:Source |
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| has_exact_synonym |
PathwayType: signaling PMID: 18667687 CellType: cancer cell PMID: 17297502 PMID: 22417299 Notes: Headnote: Prostate cancer is a cancer that develops in the prostate gland. Prostate cancer cases are characterized by considerable heterogeneity especially during the progression to hormone-refractory status. This pathway describes the signaling cascades that could potentially exist in cancer cells, but may not necessarily occur in every case. Signaling description: It is generally accepted that androgen receptor (AR) plays a significant role in prostate cancer even upon transition to an androgen-independent state. This may be due to changes in either the receptor itself (e.g., mutations or amplifications) or in coregulators influencing AR activity (e.g., NCOA2, NCOA3, NCOA4, CCND1, and ARA55). However, in primary tumors AR activity is strongly dependent on androgens (testosterone and DHT) and antiandrogen therapy is used successfully to stop the progression of the cancer. Nevertheless, during this therapy the disease acquires androgen-refractory status characterized by deregulation of many signaling pathways. One of the deregulated signaling cascades in prostate cancer cells is the PI3K/Akt pathway that is found to be highly activated in advanced cases of the disease. The main cause of constitutive activation of Akt (AKT1) is the loss of PTEN function in advanced cancer since PI3K pathway inhibition is primarily performed by the tumor suppressor, PTEN. Another signaling cascade that is deregulated in prostate cancer is MAP kinase (MAPK) pathway. The main probable cause for permanent activation of the MAPK cascade in prostate cancer cells is increased levels of autocrine and paracrine growth factors. Additionally, prostate cancer cells are characterized by the overexpression of some growth factor receptors (e.g., ERBB2), that also activate growth factor pathways. Multiple growth factors and cytokines such as epidermal growth factor (EGF), insulin-like growth factor-1 (IGF1), and interleukin-6 (IL6) stimulate cell growth through the activation of small G-protein Ras and MAPK cascade. The phosphorylation of ERK1/2 (MAPK1/2) leads to the activation of various transcription factors such as MYC, ETS1, EGR1, SP1, and Jun/Fos and the modulation of downstream cell processes. In addition, the transmembrane receptor tyrosine kinase, c-Met (MET) plays an important role in prostate cancer. MET is activated by the hepatocyte growth factor/scatter factor (HGF/SF), which is a multifunctional growth factor that regulates various cell processes such as cell motility, invasive growth, and angiogenesis. AR inhibits the expression of MET by competing with another transcription factor, SP1 for binding to the promoter of MET gene. Lastly, there are several microRNAs (miRNAs) that play a major role in the pathogenesis and prognosis of prostate cancer. Several miRNAs and their targets have been discovered to express abnormally in some prostate cancer cases, including some that are oncogenic (MIR106B and MIR221) and tumor suppressive (MIR15A, MIR145, and MIR101-1). Outcome effects: AKT1 regulates cell survival and cell cycle. For example, AKT1 negatively regulates apoptosis by inhibiting procaspase-9 (CASP9) and BAD, while positively regulating the cell cycle by inhibiting p21 and p27, thus enabling cell cycle progression. Furthermore, AKT1 can also regulate AR activity. In the normal prostate, AR seems to balance proliferative and proapoptotic programs, while in cancerous tissue AKT1 can phosphorylate and inactivate AR, thereby permanently switching on a pro-survival program. Another target of AKT1 is enhancer of zeste homolog 2 (EZH2), which is a transcriptional repressor whose expression in prostate cancer is associated with hormone-refractory status and metastasis. Further, the MAPK pathway controls such processes as proliferation, metastasis, and angiogenesis as well as resistance to antitumor drugs. One of the transcriptional targets of MAPK signaling is interleukin-6 which can play a role in the progression of prostate cancer through sev Description: Prostate cancer cases are characterized by considerable heterogeneity especially during the progression to hormone-refractory status. Pathway is built manually using published studies. PMID: 21475371 Organ: prostate NodeType: Pathway PMID: 21956922 Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin PMID: 16741972 Organ_System: urinary tract Source: Diseases |
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| id |
urn:agi-pathway:uuid-a97ac062-8753-4ba3-afc5-3caa86b6ca97 |
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| label |
Prostate Cancer |
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| notation |
uuid-a97ac062-8753-4ba3-afc5-3caa86b6ca97 |
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| prefLabel |
Prostate Cancer |
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| treeView |
urn:agi-folder:urinary_tract urn:agi-folder:p urn:agi-folder:prostate_cancer |
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| subClassOf |
urn:agi-folder:urinary_tract urn:agi-folder:p urn:agi-folder:prostate_cancer |