{"id":865,"date":"2016-12-18T16:05:06","date_gmt":"2016-12-18T16:05:06","guid":{"rendered":"http:\/\/biodigestor.net\/?p=865"},"modified":"2016-12-18T16:05:06","modified_gmt":"2016-12-18T16:05:06","slug":"insulin-like-growth-factor-igf-system-plays-important-roles-in-carcinogenesis-and","status":"publish","type":"post","link":"https:\/\/biodigestor.net\/?p=865","title":{"rendered":"Insulin-like growth factor (IGF) system plays important roles in carcinogenesis and"},"content":{"rendered":"

Insulin-like growth factor (IGF) system plays important roles in carcinogenesis and maintenance of the malignant phenotype. phosphatidylinositol 3-kinase and mitogen-activated protein kinase were involved in IGF-I induction of SNCG expression. Interestingly SNCG knockdown led to proteasomal degradation of IGF-IR thereby decreasing the steady-state levels of IGF-IR. Silencing of SNCG resulted in a decrease in ligand-induced phosphorylation of IGF-IR and its downstream signaling components including insulin receptor substrate (IRS) Akt and ERK1\/2. Strikingly SNCG physically interacted with IGF-IR and IRS-2. Silencing of IRS-2 impaired the interaction between SNCG and IGF-IR. Finally SNCG knockdown suppressed IGF-I-induced cell proliferation and migration. These data reveal that SNCG and IGF-IR are mutually regulated by each other. SNCG blockade may suppress IGF-I-induced cell proliferation and migration. Conversely IGF-IR inhibitors may be of utility in suppressing the aberrant expression of SNCG in cancer cells and thereby block its pro-tumor effects. (16) found that an increase in growth hormone and IGF-I during adolescence in these rats led to a 25% increase in tumor incidence. In addition IGF-IR expression and kinase activity are elevated in various tumors (17 -19). Regulation of IGF-IR expression and activity may dictate cell fate cell cycle arrest proliferation or apoptosis. IGF-IR may promote tumor progression by stimulating tumor growth angiogenesis and metastasis (20). Blockade of IGF-IR inhibits tumorigenesis and metastasis (21 22 The synucleins are a group of proteins that have been implicated in human diseases such as neurodegenerative diseases ocular diseases and cancer (23). The synuclein family consists of \u03b1- \u03b2- and \u03b3-synucleins. (+)-Corynoline \u03b1-Synuclein is closely linked to Parkinson disease Alzheimer disease dementia with Lewy bodies multiple system atrophy and neurodegeneration with brain iron accumulation type 1 (24). \u03b2-Synuclein and \u03b3-synuclein (SNCG) however possess antagonistic properties to \u03b1-synuclein. is expressed in peripheral neurons (25). Thus far the physiological function of SNCG remains largely unknown. Aberrant expression of SNCG is found in the majority of late-stage of breast and ovarian carcinoma as well as in liver cancer gastric cancer and pancreatic cancer (26 -30). Overexpression of SNCG in breast cancer colon cancer and pancreatic carcinoma may serve as a (+)-Corynoline<\/a> prognostic marker (29 31 32 As a multifunctional protein SNCG reportedly stimulates cancer metastasis (29 33 impairs cell cycle checkpoint (34) promotes cancer cell proliferation and survival (35 -37) and mediates chemotherapeutic drugs resistance (38). These data suggest that SNCG may be a proto-oncogene that promotes tumor progression and hence a potential molecular target for cancer therapy. Here we report that SNCG is involved in IGF-I signaling. IGF-I induces SNCG expression in different (+)-Corynoline types of cancer cells. SNCG physically interacts with IGF-IR and IRS-2. IRS-2 mediates the interaction between SNCG and IGF-IR. SNCG knockdown results in proteasomal degradation of IGF-IR and a decrease in IGF-I-induced (+)-Corynoline phosphorylation of IGF-IR and its downstream signaling components including IRS-1 Akt and ERK1\/2. SNCG blockade suppresses IGF-I-induced cellular proliferation and migration. EXPERIMENTAL PROCEDURES Reagents and Antibodies IGF-I was purchased from PeproTech Inc. (Rocky Hill NJ) and prepared by reconstituting in deionized water and by diluting to the appropriate concentration in Dulbecco’s minimal essential medium (DMEM) and stored HHEX<\/a> at ?20 \u00b0C. Mitomycin C 5 and tyrphostin AG1024 were purchased from Sigma. The PI3K inhibitor LY294002 MAPK\/ERK kinase (MEK) inhibitor U0126 anti-GRP78 anti-IGF-IR\u03b2 anti-phosphorylated IGF-IR\u03b2 (Tyr-1131) anti-Akt and phosphorylated Akt (Ser-473) anti-ERK1\/2 and phosphorylated ERK1\/2 antibodies were purchased from Cell Signaling Technology (Beverly MA). Another IGF-IR antibody for immunoprecipitation was from Abcam Ltd. (Shatin N.T. Hong Kong). Anti-IRS-1 anti-IRS-2 and anti-phosphorylated IRS-1 (Tyr-896) antibodies were from Epitomics (Burlingame CA). Anti-SNCG antibody and anti-actin antibody were from Santa Cruz Biotechnology (Santa Cruz.<\/p>\n","protected":false},"excerpt":{"rendered":"

Insulin-like growth factor (IGF) system plays important roles in carcinogenesis and maintenance of the malignant phenotype. phosphatidylinositol 3-kinase and mitogen-activated protein kinase were involved in IGF-I induction of SNCG expression. Interestingly SNCG knockdown led to proteasomal degradation of IGF-IR thereby decreasing the steady-state levels of IGF-IR. Silencing of SNCG resulted in a decrease in ligand-induced… Continue reading Insulin-like growth factor (IGF) system plays important roles in carcinogenesis and<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[72],"tags":[825,826],"class_list":["post-865","post","type-post","status-publish","format-standard","hentry","category-activin-receptor-like-kinase","tag-corynoline","tag-hhex","entry"],"_links":{"self":[{"href":"https:\/\/biodigestor.net\/index.php?rest_route=\/wp\/v2\/posts\/865"}],"collection":[{"href":"https:\/\/biodigestor.net\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biodigestor.net\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biodigestor.net\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/biodigestor.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=865"}],"version-history":[{"count":1,"href":"https:\/\/biodigestor.net\/index.php?rest_route=\/wp\/v2\/posts\/865\/revisions"}],"predecessor-version":[{"id":866,"href":"https:\/\/biodigestor.net\/index.php?rest_route=\/wp\/v2\/posts\/865\/revisions\/866"}],"wp:attachment":[{"href":"https:\/\/biodigestor.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=865"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biodigestor.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=865"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biodigestor.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=865"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}