An emerging strategy for cancer treatment targeting aberrant glycogen synthase kinase 3 beta
Improvement in the outcome of cancer patients who are refractory to currently available treatments relies on the development of target-directed therapies. One group of molecular targets with potential clinical relevance is a set of protein tyrosine kinases encoded mostly by proto-oncogenes and that are frequently deregulated in cancer. Glycogen synthase kinase 3beta (GSK3beta), a serine/threonine protein kinase, has emerged as a therapeutic target for common chronic diseases including type 2 diabetes mellitus, neurodegenerative disorders, inflammation and osteoporosis. This is based on its currently known functions and primary pathologic causalities. GSK3beta has well characterized roles in the regulation of gene transcription and in oncogenic signaling. We have shown that deregulated GSK3beta promotes gastrointestinal, pancreatic and liver cancers and glioblastomas. Furthermore, we have demonstrated that inhibition of GSK3beta attenuates cell survival and proliferation, induces cell senescence and apoptosis and sensitizes tumor cells to chemotherapeutic agents and ionizing radiation. This has led us to propose GSK3beta as a potential therapeutic target in cancer. The anti-tumor effects of GSK3beta inhibition are mediated by changes in the expression and phosphorylation of molecules critical to the regulation of cell cycling, proliferation and apoptosis and underlie the pathological role for GSK3beta in cancer. Investigation of the mechanisms responsible for deregulation of GSK3beta and the consequent downstream pathologic effects in cancer cells has shed light on the molecular pathways leading to tumorigenesis. This will allow exploration of novel therapeutic strategies for cancer that target aberrant GSK3beta.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2009 |
|---|---|
| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
|---|---|
| Enthalten in: |
Anti-cancer agents in medicinal chemistry - 9(2009), 10 vom: 01. Dez., Seite 1114-22 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Miyashita, Katsuyoshi [VerfasserIn] |
|---|
| Anmerkungen: |
Date Completed 05.11.2010 Date Revised 27.10.2019 published: Print Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM192938983 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM192938983 | ||
| 003 | DE-627 | ||
| 005 | 20231223193855.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231223s2009 xx |||||o 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0643.xml |
| 035 | |a (DE-627)NLM192938983 | ||
| 035 | |a (NLM)19925395 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Miyashita, Katsuyoshi |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An emerging strategy for cancer treatment targeting aberrant glycogen synthase kinase 3 beta |
| 264 | 1 | |c 2009 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 05.11.2010 | ||
| 500 | |a Date Revised 27.10.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Improvement in the outcome of cancer patients who are refractory to currently available treatments relies on the development of target-directed therapies. One group of molecular targets with potential clinical relevance is a set of protein tyrosine kinases encoded mostly by proto-oncogenes and that are frequently deregulated in cancer. Glycogen synthase kinase 3beta (GSK3beta), a serine/threonine protein kinase, has emerged as a therapeutic target for common chronic diseases including type 2 diabetes mellitus, neurodegenerative disorders, inflammation and osteoporosis. This is based on its currently known functions and primary pathologic causalities. GSK3beta has well characterized roles in the regulation of gene transcription and in oncogenic signaling. We have shown that deregulated GSK3beta promotes gastrointestinal, pancreatic and liver cancers and glioblastomas. Furthermore, we have demonstrated that inhibition of GSK3beta attenuates cell survival and proliferation, induces cell senescence and apoptosis and sensitizes tumor cells to chemotherapeutic agents and ionizing radiation. This has led us to propose GSK3beta as a potential therapeutic target in cancer. The anti-tumor effects of GSK3beta inhibition are mediated by changes in the expression and phosphorylation of molecules critical to the regulation of cell cycling, proliferation and apoptosis and underlie the pathological role for GSK3beta in cancer. Investigation of the mechanisms responsible for deregulation of GSK3beta and the consequent downstream pathologic effects in cancer cells has shed light on the molecular pathways leading to tumorigenesis. This will allow exploration of novel therapeutic strategies for cancer that target aberrant GSK3beta | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Review | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a GSK3B protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Glycogen Synthase Kinase 3 beta |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Glycogen Synthase Kinase 3 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.26 |2 NLM | |
| 700 | 1 | |a Nakada, Mitsutoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Shakoori, Abbas |e verfasserin |4 aut | |
| 700 | 1 | |a Ishigaki, Yasuhito |e verfasserin |4 aut | |
| 700 | 1 | |a Shimasaki, Takeo |e verfasserin |4 aut | |
| 700 | 1 | |a Motoo, Yoshiharu |e verfasserin |4 aut | |
| 700 | 1 | |a Kawakami, Kazuyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Minamoto, Toshinari |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Anti-cancer agents in medicinal chemistry |d 2006 |g 9(2009), 10 vom: 01. Dez., Seite 1114-22 |w (DE-627)NLM160693403 |x 1875-5992 |7 nnns |
| 773 | 1 | 8 | |g volume:9 |g year:2009 |g number:10 |g day:01 |g month:12 |g pages:1114-22 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 9 |j 2009 |e 10 |b 01 |c 12 |h 1114-22 | ||