Journal
PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES
Volume 98, Issue 2, Pages 72-86Publisher
JAPAN ACAD
DOI: 10.2183/pjab.98.005
Keywords
GSTP1; KRAS cancer; BRAF cancer; MAPK signaling; drug resistance; tumor marker
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Funding
- Shonan Kamakura General Hospital
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GSTP1, a glutathione-S transferase isozyme, is highly expressed in malignant tissues and serves as a tumor marker and a refractory factor against certain types of anticancer drugs. Recent studies have also identified its chaperone activity in regulating intracellular protein function.
Glutathione-S transferase P1 (GSTP1) is one of the glutathione-S transferase isozymes that belong to a family of phase II metabolic isozymes. The unique feature of GSTP1 compared with other GST isozymes is its relatively high expression in malignant tissues. Thus, clinically, GSTP1 serves as a tumor marker and as a refractory factor against certain types of anticancer drugs through its primary function as a detoxifying enzyme. Additionally, recent studies have identified a chaperone activity of GSTP1 involved in the regulation the function of various intracellular proteins, including factors of the growth signaling pathway. In this review, we will first describe the function of GSTP1 and then extend the details onto its role in the mitogen-activated protein kinase signal pathway, referring to the results of our recent study that proposed a novel autocrine signal loop formed by the CRAF/GSTP1 complex in mutated KRAS and BRAF cancers. Finally, the possibilities of new therapeutic approaches for these cancers by targeting this complex will be discussed.
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