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Query: UMLS:C0476089 (
endometrial cancer
)
11,379
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
This study evaluated the potential ability of MK-0646 to inhibit IGF1-mediated biological actions and cell signaling events in Type 1 and Type 2
endometrial cancer
. We found that MK-0646 treatment significantly decreased
IGF1R
expression. In addition, pretreatment with MK-0646 decreased the IGF1-induced phosphorylation of
IGF1R
, AKT and ERK. Apoptosis analyses showed that MK-0646 abolished the anti-apoptotic effect of IGF1. Furthermore, MK-0646 treatment abolished the IGF1-stimulatory effect on proliferation and enhanced the cytotoxic effect of cisplatin. These findings indicate that specific inhibition of
IGF1R
could be a useful therapeutic approach for Type 1 and Type 2
endometrial cancer
.
...
PMID:IGF1R-directed targeted therapy enhances the cytotoxic effect of chemotherapy in endometrial cancer. 2340 16
N6-methyladenosine (m
6
A) messenger RNA methylation play important role in cell proliferation and tumorigenicity of
endometrial cancer
, but the key mechanism is not fully clear. Here, we found that RNA demethylase ALKBH5 expression was significantly upregulated in
endometrial cancer
, ALKBH5 was then identified to positively regulate proliferation and invasion of
endometrial cancer
. Mechanistically, the m
6
A eraser ALKBH5 demethylated target transcripts
IGF1R
and enhanced
IGF1R
mRNA stability, consequently promoting
IGF1R
translation and activating
IGF1R
signaling pathway. Thus, we demonstrated that ALKBH5 promoted proliferation and invasion of
endometrial cancer
via erasing
IGF1R
m
6
A-modifications, which suggests a potential therapeutic target for
endometrial cancer
.
...
PMID:ALKBH5 regulates IGF1R expression to promote the Proliferation and Tumorigenicity of Endometrial Cancer. 3291 56
Endometrial carcinoma
(EC) is the most common gynecologic malignancy in the United States, with limited effective targeted therapies. Endometrial tumors exhibit frequent alterations in protein kinases, yet only a small fraction of the kinome has been therapeutically explored. To identify kinase therapeutic avenues for EC, we profiled the kinome of endometrial tumors and normal endometrial tissues using Multiplexed Inhibitor Beads and Mass Spectrometry (MIB-MS). Our proteomics analysis identified a network of kinases overexpressed in tumors, including Serine/Arginine-Rich Splicing Factor Kinase 1 (SRPK1). Immunohistochemical (IHC) analysis of endometrial tumors confirmed MIB-MS findings and showed SRPK1 protein levels were highly expressed in endometrioid and uterine serous cancer (USC) histological subtypes. Moreover, querying large-scale genomics studies of EC tumors revealed high expression of SRPK1 correlated with poor survival. Loss-of-function studies targeting SRPK1 in an established USC cell line demonstrated SRPK1 was integral for RNA splicing, as well as cell cycle progression and survival under nutrient deficient conditions. Profiling of USC cells identified a compensatory response to SRPK1 inhibition that involved EGFR and the up-regulation of
IGF1R
and downstream AKT signaling. Co-targeting SRPK1 and EGFR or
IGF1R
synergistically enhanced growth inhibition in serous and endometrioid cell lines, representing a promising combination therapy for EC.
...
PMID:Kinome Profiling of Primary Endometrial Tumors Using Multiplexed Inhibitor Beads and Mass Spectrometry Identifies SRPK1 as Candidate Therapeutic Target. 3299 15
