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Reverse Phase Protein Array (RPPA) profiling of cell signaling events in MDA-MB-468 cells and PC-3 cells treated with Akt PROTAC degrader-MS21

ABSTRACT: Reverse Phase Protein Array (RPPA) profiling of cell signaling events in MDA-MB-468 cells and PC-3 cells treated with Akt PROTAC degrader-MS21

PROVIDER: PRJNA591944 | ENA |

REPOSITORIES: ENA

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Reverse Phase Protein Array (RPPA) profiling of cell signaling events in MDA-MB-468 cells and PC-3 cells treated with Akt PROTAC degrader-MS21

Project description:To compare the cell signaling events between PC-3 cells and MDA-MB-468 cells, we performed a Reverse Phase of Protein Array (RPPA) profiling on 468 and PC-3 Cells that treated with DMSO, AZD5363, MS21 at 1µM for 24hr respectively.

2019-11-27 | GSE141079 | GEO

Reverse Phase Protein Array (RPPA) profiling of cell signaling events in 468 cells induced by PTEN overexpression or PTEN-Long overexpression

Project description:To investigate the novel functions of PTEN-L, we performed a Reverse Phase of Protein Array (RPPA) profiling on 468.Ctrl, 468.PTEN, and 468.PTEN-L sublines to compare cell signaling events between PTEN expression

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Discovery of 180055 as a PROTAC degrader for Treating Cancers

Project description:PARP1 is an abundant nuclear protein that is involved in a number of biological processes linked to cellular stress responses. PARP1 inhibitors (PARPi) are known to kill tumor cells via two mechanisms (PARP1 catalytic inhibition and PARP1 trapping). In this work we discovered a PROTAC degrader of PARP1 -180055, which uncoupled PARP1 trapping and inhibition. Moreover, 180055 has great potential for treating cancers.

2023-05-18 | PXD042311 | iProX

Selective PROTAC-mediated degradation and shRNA-driven knockdown of SMARCA2 in HCC2302 lung adenocarcinoma cells

Project description:SMARCA2 and SMARCA4 are mutually-exclusive, core catalytic subunits for the chromatin remodeling SWI/SNF complex. Mutations in SMARCA4 are common in lung adenocarcinoma and have shown synthetic lethality with loss of SMARCA2 loss of function. The purpose of this project is to answer questions related to the in vivo [mouse xenograft] efficacy of A947, a SMARCA2 degrader. The study involves in vitro versus in vivo comparisons of drug activity, in addition to genetic manipulation of the target. Model system: HCC2302 (RRID:CVCL_V636); Model origin: Lung Adenocarcinoma; Perturbation: A947 (VHL-PROTAC-based degrader)

2022-06-13 | GSE205542 | GEO

I-SPY2-990 mRNA/RPPA Data Resource: RPPA component

Project description:I-SPY2-990 mRNA/RPPA Data Resource: RPPA component

| PRJNA803248 | ENA

I-SPY2-990 mRNA/RPPA Data Resource: RPPA component

Project description:The RPPA component of the I-SPY2-990 mRNA/RPPA Data Resource contains protein/phosphoprotein data from pre-treatment laser capture microdissected (LCM) tumor biopsies for 139 key signaling proteins/phosphoproteins in cancer for 736 patients from 8 arms of the neoadjuvant I-SPY2 TRIAL (NCT01042379) for aggressive early stage breast cancer [194 Control (Ctr); 63 veliparib/carboplatin (VC); 105 neratinib (N); 87 MK2206; 128 trebananib; 49 TDM1/pertuzumab(P); 43 H/P; and 67 pembrolizumab (pembro)]. This record also contains clinical data for these patients, including HR, HER2 and MP status, response (pCR or no pCR), and treatment arm. RPPA endpoints assayed are from hormone receptor (n=4), HER family (n=14), cell cycle/proliferation (n=20), immune (n=18), DNA repair deficiency (DDR; n=15), AKT/mTOR/PI3K (n=7), apoptosis/autophagy (n=10), IGF1R (n=6), TIE/ANG (n=4), growth/survival/metabolism (n=22) and RTK (n=19) pathways. For gene expresson data for all 736 patients with RPPA data, plus an additional 150 patients for a total 987 patients from 10 arms of I-SPY2 (mRNA component of the I-SPY2-990 Data Resource), see the companion GEO record/subseries GSE194040.

2022-05-25 | GSE196093 | GEO

Reverse Phase Protein Array (RPPA) profiling of cell signaling events in 468 cells induced by PTEN overexpression or PTEN-Long overexpression

Project description:Reverse Phase Protein Array (RPPA) profiling of cell signaling events in 468 cells induced by PTEN overexpression or PTEN-Long overexpression

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Project description:HDAC3 and HDAC8 are members of class I deacetylases involved in several biological mechanisms and represent a highly sought-after therapeutic target for drug development. It is historically challenging to develop selective deacetylase inhibitors due to their conserved catalytic domains. HDAC3 also has deacetylase-independent activity, which cannot be blocked by conventional enzymatic inhibitors. Recent advance in proteolysis-targeting chimeras (PROTACs) provides an opportunity to eliminate the whole protein selectively, abolishing both enzymatic and scaffolding function. Here, we report a novel HDAC3/8 dual degrader YX968 that induces highly potent, rapid, and selective degradation of both HDAC3 and HDAC8 without trigging pan-HDAC inhibitory effects. Unbiased quantitative proteomics experiments further confirmed its high selectivity. This dual-specific degrader specifically ablates cellular pathways attributed to HDAC3 and HDAC8 and exhibits high potency in killing cancer cells. YX968 represents a new probe for dissecting the complex biological functions of HDAC3 and HDAC8.

2023-07-18 | GSE211758 | GEO

Androgen receptor-negative prostate cancer is vulnerable to SWI/SNF-targeting degrader molecules

Project description:The switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex becomes frequently deregulated in advanced castration-resistant prostate cancer (CRPC). SWI/SNF ATPase degrader molecules, also known as Proteolysis targeting chimera (PROTAC), offer a novel approach to tackle resistance to androgen receptor (AR) antagonists in AR-dependent CRPC (CRPC-AR). However, the frequent emergence of AR-negative CRPC remains a major clinical hurdle. We investigated SWI/SNF ATPase targeting agents in AR-negative CRPC. SWI/SNF targeting PROTAC treatment reduced the viability of both CRPC-AR and WNT-signaling dependent CRPC (CRPC-WNT), which accounts for about 10% of all clinical CRPC cases. In CRPC-WNT, we characterized that SWI/SNF ATPase SMARCA4 depletion interfered with WNT signaling via the master transcriptional regulator TCF7L2 (TCF4). Functionally, TCF7L2 maintains proliferation via the AP-1/MAPK signaling axis in this subtype of CRPC.

2024-03-18 | GSE261446 | GEO

I-SPY2-990 mRNA/RPPA Data Resource

Project description:The I-SPY2-990 mRNA/RPPA data resource contains gene expression, protein/phosphoprotein and clinical data for ~990 patients from the first 10 completed arms of the I-SPY 2 platform trial for aggressive, early stage breast cancer. Experimental treatments include pan-HER2 inhibitors and anti-HER2 agents, PARP inhibitor/DNA damaging agent combinations, an AKT inhibitor, immunotherapy, and ANG1/2, IGF1R and HSP90 inhibitors added to standard of care chemotherapy. All patients have pretreatment full transcriptome expression data on over ~19,000 genes assayed on Agilent 44K. 736 patients (all arms except ganitumab and ganetespib) have normalized LCM-RPPA data for 139 key signaling proteins/phosphoproteins in cancer. Clinical data includes HR, HER2 and MP status, response (pCR or no pCR), and treatment arm. This SuperSeries is composed of the mRNA and RPPA SubSeries listed below.

2022-05-25 | GSE196096 | GEO

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