Targeting the Raft-Associated Akt Signaling in Hepatocellular Carcinoma

Abstract

Caveolin-1 and flotillin-1 are considered as markers of lipid rafts which can be regarded as sorting platforms for targeted transport of transmembrane proteins and are involved in fundamental cellular events such as signal transduction, cell adhesion, lipid/protein sorting, and human cancer. We addressed caveolin-1 and flotillin-1 expression in 90 human hepatocellular carcinoma (HCC) and adjacent noncancerous tissues (ANT) samples by SDS-PAGE and immunoblotting with specific antibodies. Significant caveolin-1 and flotillin-1 overexpression was found in HCC tissues compared to ANT and was confirmed by immunohistochemistry. Raft-associated Akt signaling pathway components involved in the regulation of cell survival were altered by western blotting in HCC microdomain-enriched subcellular fractions purified from paired HCC and ANT samples. Our results demonstrated that the activity of raft-associated but not total membrane Akt determines its cellular functions. Lipid rafts differ in different types of tissues, which allows for the possibility of tissue-type-specific targeting for cell survival.

Feeding-fasting dependent recruitment of membrane microdomain proteins to lipid droplets purified from the liver

“…IHC on liver sections was done following a published protocol [ 56 ]. Whole body perfusion of anaesthetised animals was done using normal saline for 15 minutes, followed by 4% PFA, till full body twitching and clearance of the tissue was observed.…”

Antioxidant and Anticancer Roles of a Novel Strain ofBacillus anthracisIsolated from Vermicompost Prepared from Paper Mill Sludge

“…PI 3K phosphorylates phosphatidyl inositol and helps in attachment and activation of second messengers that control cellular activities and properties including proliferation, survival, and motility [ 36 , 37 ]. Akt is one of the secondary downstream messenger protein which gets activation upon phosphorylation [ 38 ]. Phosphorylation of Akt leads to inhibition of proapoptotic signal as well as increase in antiapoptotic molecule [ 39 ].…”

“…Fragmentation analysis along with activity staining of SOD proves that crude ethyl acetate extract was efficient in killing cancer cells [ 41 ]. Earlier findings reported that decrease in Akt level and increase in SOD may be due to enhanced activity of PTEN tumor suppressor [ 38 ]. It can be assumed that the triggering factor is the degradation of NF κ -B which leads to the change in oxidative stress of MCF-7 cells upon treatment of extract [ 42 – 44 ].…”

The Hypoxic Tumor Microenvironment Promotes Invadopodia Formation and Metastasis through LPA1 Receptor and EGFR Cooperation

“…Hypoxia has been reported to rapidly increase cellular cholesterol levels, thereby influencing the composition, number, and size of lipid rafts (41). Lipid rafts function as organizing centers for the assembly of signaling molecules; their increased rigidity optimizes spatiotemporal interactions and compartmentalizes proteins involved in specific signaling tasks (42,43). Interestingly, both RTKs and GPCRs can localize to lipid rafts, which provide a platform that facilitates interactions between EGFR and GPCRs, therefore enhancing the efficiency of transactivation (44).…”

“…Interestingly, both RTKs and GPCRs can localize to lipid rafts, which provide a platform that facilitates interactions between EGFR and GPCRs, therefore enhancing the efficiency of transactivation (44). Lipid rafts have also been identified as key plasma membrane microdomains for Src-EGFR functional interactions as well as PI3K/Akt activation (42,45). It is therefore conceivable that, under hypoxic conditions, the recruitment of LPA 1 , Src, and EGFR in lipid rafts facilitates their interactions and that results in prolonged Akt activation and invadopodia formation.…”