AKT Activation and Telomerase Reverse Transcriptase Expression are Concurrently Associated with Prognosis of Gastric Cancer

Sasaki, Takuma; Kuniyasu, Hiroki; Luo, Yi; Kitayoshi, Misaho; Tanabe, Eriko; Kato, Daisuke; Shinya, Satoshi; Fujii, Kenichi; Ohmori, Hitoshi; Yamashita, Yuichi

doi:10.1159/000351721

Cited by 31 publications

(23 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…our data showed that aKt and htert were widely expressed in gastric cancer. the concurrent expression of these two proteins at high levels is associated with a poor prognosis (31). these results suggest that aKt and htert are good molecular targets, and that inhibiting them could be useful for the treatment of gastric cancer ( fig.…”

Section: The Concurrent Effects Of Pakt and Htert On The Progression mentioning

confidence: 81%

Significance of AKT in gastric cancer (Review)

Sasaki

Kuniyasu

2014

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

Abstract. aKt is a serine/threonine kinase activated downstream of integrin, which is a receptor for various pro-proliferation and bioactive substances as well as the extracellular matrix receptor. the activation of aKt often contributes to tumorigenesis and plays a role in regulating cell motility, which is critical for local invasion and metastasis. in recent years, it has also drawn attention as a target of new molecular-targeted agents. When analyzing the role of aKt in cancer cells, it is important to consider the microenvironment and variations of cancers. in this review, a basic overview of the role of aKt in normal and malignant tissues is provided, along with an in-depth discussion of its role in gastric cancer and its potential as a target for therapy. Contents1. introduction 2. What is aKt? 3. aKt and the pro-survival effect 4. aKt signal transduction in cancer cells 5. the activion of various cancer cells by aKt 6. the Pi3K-aKt-mtor pathway and its activation in gastric cancer 7. htert 8. the concurrent effects of paKt and htert on the progression of gastric cancer 9. relationships among the levels of paKt and inoS, nt and htert in gastric mucosa 10. conclusion IntroductionaKt signaling pathways are related to the suppression of apoptosis, proliferation and metastasis of cells, angiogenesis and various other processes (1). aKt is involved in the proliferation of cells via its phosphorylation of cyclin D1, and promotes the phosphorylation of BaD and caspase-9 which is associated with apoptosis. By inhibiting these molecules (BaD and caspase-9), aKt suppresses apoptosis. aKt plays an important role in the chemosensitivity to various agents, because it prevents the normal apoptotic response to treatment. aKt is also deeply involved in angiogenesis and the invasion of cancer cells into surrounding tissues through vascular endothelial growth factor (Vegf) and MMP (2,3). the mechanism regulating phosphatidylinositol-3 kinase (Pi3K)/aKt has been shown to be abnormal in various solid carcinomas and hematological neoplasms. the overexpression of aKt at the Dna or protein level has been reported in breast cancer and stomach cancers (1); thus, aKt has drawn attention as a target for the development of new molecular-targeted cancer therapeutic agents. in this review, a basic overview of the role of aKt in normal and malignant tissues is provided, along with an in-depth discussion of its role in gastric cancer and its potential as a target for therapy. What is AKT?aKt is a serine/threonine kinase activated at downstream of integrin, which is a receptor for various pro-proliferation and bioactive substances (receptor tyrosine kinases and g protein-coupled receptors) as well as extracellular matrix receptor. aKt has three isoforms, with aKt1 and aKt2 being expressed ubiquitously, while the expression of aKt3 occurs in limited tissues (brain and testes). all three isoforms are composed of a pleckstrin homology (PH) domain, linker domain, kinase domain and c-terminal hydrophobic domain. following the activation of Pi...

show abstract

Section: The Concurrent Effects Of Pakt and Htert On The Progression mentioning

confidence: 81%

Significance of AKT in gastric cancer (Review)

Sasaki

Kuniyasu

2014

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The levels of pAKT or pAKT/hTERT are not associated with clinicopathological parameters, such as the tumor stage and presence of nodal metastasis. However, the survival rate of the patients with a high level of pAKT or the patients with a high level of pAKT and hTERT has been found to be significantly worse compared with other patients (43). These findings suggest that AKT and hTERT are good molecular targets for the treatment of gastric cancer.…”

Section: Telomeres and Aktmentioning

confidence: 94%

“…By contrast, AKT inactivation by inhibitors and knockdown decreased hTERT expression and telomerase activity in MKN28 gastric cancer cells (43). In 40 gastric cancer tissues, a significant association was found between the levels of pAKT and hTERT expression and telomere length (43). The levels of pAKT or pAKT/hTERT are not associated with clinicopathological parameters, such as the tumor stage and presence of nodal metastasis.…”

Section: Telomeres and Aktmentioning

confidence: 97%

“…The activation of AKT by epidermal growth factor was found to increase hTERT expression and telomerase activity. By contrast, AKT inactivation by inhibitors and knockdown decreased hTERT expression and telomerase activity in MKN28 gastric cancer cells (43). In 40 gastric cancer tissues, a significant association was found between the levels of pAKT and hTERT expression and telomere length (43).…”

Section: Telomeres and Aktmentioning

confidence: 98%

“…In a previous study, the significance of AKT phosphorylation and hTERT on the prognosis of gastric cancer was examined (43). The activation of AKT by epidermal growth factor was found to increase hTERT expression and telomerase activity.…”

Section: Telomeres and Aktmentioning

confidence: 99%

See 2 more Smart Citations

AKT plays a crucial role in gastric cancer

2015

Self Cite

View full text Add to dashboard Cite

Abstract. The AKT protein is involved in the phosphatidylinositol-3 kinase signaling pathway and is a vital regulator of survival, proliferation and differentiation in various types of cells. Helicobacter pylori infection induces epithelial cell proliferation and oxidative stress in chronic gastritis. These alterations lead to telomere shortening, resulting in the activation of telomerase. AKT, in particular, is activated by H. pylori-induced inflammation. AKT then promotes the expression of human telomerase reverse transcriptase, which encodes a catalytic subunit of telomerase, and induces telomerase activity, an essential component of the process of carcinogenesis. AKT activation is increased in gastric mucosa with carcinogenic properties and is associated with the low survival of patients with gastric cancer. The findings of the present study suggest that AKT is pivotal in gastric carcinogenesis and progression.

show abstract

Drug design targeting active posttranslational modification protein isoforms

Meng

Liang

Zhao

et al. 2020

Medicinal Research Reviews

View full text Add to dashboard Cite

Modern drug design aims to discover novel lead compounds with attractable chemical profiles to enable further exploration of the intersection of chemical space and biological space. Identification of small molecules with good ligand efficiency, high activity, and selectivity is crucial toward developing effective and safe drugs. However, the intersection is one of the most challenging tasks in the pharmaceutical industry, as chemical space is almost infinity and continuous, whereas the biological space is very limited and discrete. This bottleneck potentially limits the discovery of molecules with desirable properties for lead optimization. Herein, we present a new direction leveraging posttranslational modification (PTM) protein isoforms target space to inspire drug design termed as “Post‐translational Modification Inspired Drug Design (PTMI‐DD).” PTMI‐DD aims to extend the intersections of chemical space and biological space. We further rationalized and highlighted the importance of PTM protein isoforms and their roles in various diseases and biological functions. We then laid out a few directions to elaborate the PTMI‐DD in drug design including discovering covalent binding inhibitors mimicking PTMs, targeting PTM protein isoforms with distinctive binding sites from that of wild‐type counterpart, targeting protein‐protein interactions involving PTMs, and hijacking protein degeneration by ubiquitination for PTM protein isoforms. These directions will lead to a significant expansion of the biological space and/or increase the tractability of compounds, primarily due to precisely targeting PTM protein isoforms or complexes which are highly relevant to biological functions. Importantly, this new avenue will further enrich the personalized treatment opportunity through precision medicine targeting PTM isoforms.

show abstract

AKT Activation and Telomerase Reverse Transcriptase Expression are Concurrently Associated with Prognosis of Gastric Cancer

Cited by 31 publications

References 22 publications

Significance of AKT in gastric cancer (Review)

Significance of AKT in gastric cancer (Review)

AKT plays a crucial role in gastric cancer

Drug design targeting active posttranslational modification protein isoforms

Contact Info

Product

Resources

About