The PI3K/Akt Pathway in Tumors of Endocrine Tissues DOI Creative Commons
Helen L. Robbins, Angela Hague

Frontiers in Endocrinology, Journal Year: 2016, Volume and Issue: 6

Published: Jan. 11, 2016

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a key driver in carcinogenesis. Defects this human cancer syndromes such as Cowden's disease and Multiple Endocrine Neoplasia result tumors of endocrine tissues, highlighting its importance these types. This review explores the growing evidence from multiple animal vitro models analysis for involvement following: thyroid carcinoma subtypes, parathyroid carcinoma, pituitary tumors, adrenocortical phaeochromocytoma, neuroblastoma, gastroenteropancreatic neuroendocrine tumors. Whilst data are not always consistent, immunohistochemistry performed on tumor tissue has been used alongside other techniques to demonstrate Akt overactivation. We active potential prognostic marker PI3K therapeutic target neoplasia.

Language: Английский

Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review DOI
Keywan Mortezaee, Masoud Najafi, Bagher Farhood

et al.

Life Sciences, Journal Year: 2019, Volume and Issue: 228, P. 228 - 241

Published: May 8, 2019

Language: Английский

Citations

118

Regulation of Wnt Signaling through Ubiquitination and Deubiquitination in Cancers DOI Open Access
Hong‐Beom Park, Ju-Won Kim, Kwang‐Hyun Baek

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(11), P. 3904 - 3904

Published: May 30, 2020

The Wnt signaling pathway plays important roles in embryonic development, homeostatic processes, cell differentiation, polarity, proliferation, and migration via the β-catenin binding of target genes. Dysregulation is associated with various diseases such as cancer, aging, Alzheimer's disease, metabolic pigmentation disorders. Numerous studies entailing have been conducted for cancers. Diverse factors mediate up- or down-regulation through post-translational modifications (PTMs), aberrant regulation several different malignancies humans. Of numerous PTMs involved, most are regulated by ubiquitination deubiquitination. Ubiquitination E3 ligase attaches ubiquitins to proteins usually induces proteasomal degradation β-catenin, Axin, GSK3, Dvl. Conversely, deubiquitination induced deubiquitinating enzymes (DUBs) detaches modulates stability factors. In this review, we discuss effects on pathway, inhibitors DUBs that can be applied cancer therapeutic strategies.

Language: Английский

Citations

118

The therapeutic potential of mTOR inhibitors in breast cancer DOI Open Access

Linda S. Steelman,

Alberto M. Martelli, Lucio Cocco

et al.

British Journal of Clinical Pharmacology, Journal Year: 2016, Volume and Issue: 82(5), P. 1189 - 1212

Published: April 10, 2016

Rapamycin and modified rapamycins (rapalogs) have been used to prevent allograft rejection after organ transplant for over 15 years. The mechanistic target of rapamycin (mTOR) has determined be a key component the mTORC1 complex which consists serine/threonine kinase TOR at least five other proteins are involved in regulating its activity. Some best characterized substrates kinases regulation cell growth (e.g., p70S6K) protein translation 4E‐BP1). These may some cases serve as indicators sensitivity rapamycin‐related therapies. Dysregulation activity frequently occurs due mutations at, or amplifications of, upstream factor receptors human epidermal receptor‐2, HER2) well PI3K) phosphatases PTEN) critical growth. More recently, it shown that certain rapalogs enhance effectiveness hormonal‐based therapies breast cancer patients who become resistant endocrine therapy. combined treatment everolimus) aromatase inhibitors exemestane) approved by United States Food Drug Administration (US FDA) drug regulatory agencies treat estrogen receptor positive (ER+) progressed. This review will summarize recent basic clinical research area evaluate potential novel therapeutic approaches.

Language: Английский

Citations

115

FAK/PYK2 promotes the Wnt/β-catenin pathway and intestinal tumorigenesis by phosphorylating GSK3β DOI Creative Commons
Chenxi Gao, Guangming Chen,

Shih–Fan Kuan

et al.

eLife, Journal Year: 2015, Volume and Issue: 4

Published: Aug. 14, 2015

Aberrant activation of Wnt/β-catenin signaling plays an unequivocal role in colorectal cancer, but identification effective Wnt inhibitors for use cancer remains a tremendous challenge. New insights into the regulation this pathway could reveal new therapeutic point intervention, therefore are greatly needed. Here we report novel FAK/PYK2/GSK3βY216/β-catenin axis: FAK and PYK2, elevated adenomas APCmin/+ mice human tissues, functioned redundantly to promote by phosphorylating GSK3βY216 reinforce output—β-catenin accumulation intestinal tumorigenesis. We previously showed that Wnt-induced β-catenin requires GSK3β/β-TrCP interaction; current study revealed phosphorylation was molecular determinant GSK3β recruitment β-TrCP. Pharmacological inhibition FAK/PYK2 suppressed adenoma formation accompanied with reduced levels phospho-GSK3βY216 β-catenin, indicating FAK/PYK2/GSK3βY216 axis is critical APC driven

Language: Английский

Citations

111

The PI3K/Akt Pathway in Tumors of Endocrine Tissues DOI Creative Commons
Helen L. Robbins, Angela Hague

Frontiers in Endocrinology, Journal Year: 2016, Volume and Issue: 6

Published: Jan. 11, 2016

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a key driver in carcinogenesis. Defects this human cancer syndromes such as Cowden's disease and Multiple Endocrine Neoplasia result tumors of endocrine tissues, highlighting its importance these types. This review explores the growing evidence from multiple animal vitro models analysis for involvement following: thyroid carcinoma subtypes, parathyroid carcinoma, pituitary tumors, adrenocortical phaeochromocytoma, neuroblastoma, gastroenteropancreatic neuroendocrine tumors. Whilst data are not always consistent, immunohistochemistry performed on tumor tissue has been used alongside other techniques to demonstrate Akt overactivation. We active potential prognostic marker PI3K therapeutic target neoplasia.

Language: Английский

Citations

111