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The effect of knockdown Abl kinases on breast cancer cells' global transcriptome

ABSTRACT: To gain insight into the signaling pathway(s) required for ABL1/ABL2-dependent bone metastasis, we evaluated the consequences of single or double inactivation of ABL1 and ABL2 on the transcriptome of breast cancer cells. Double ABL1/ABL2 knockdown was required to decrease the levels of p-CrKL by more than 90%, indicative of inactivation of the endogenous ABL kinases. To examine the consequences of depleting the ABL kinases on the transcriptome of metastatic breast cancer cells we employed next generation sequencing (RNAseq) analysis. We found that 180 genes were significantly down-regulated and 40 genes were significantly up-regulated in ABL1/ABL2 knockdown cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE69125 | GEO | 2016/03/02

SECONDARY ACCESSION(S): PRJNA284608

REPOSITORIES: GEO

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The effect of knockdown Abl kinases on breast cancer cells' global transcriptome

Project description:To gain insight into the signaling pathway(s) required for ABL1/ABL2-dependent bone metastasis, we evaluated the consequences of single or double inactivation of ABL1 and ABL2 on the transcriptome of breast cancer cells. Double ABL1/ABL2 knockdown was required to decrease the levels of p-CrKL by more than 90%, indicative of inactivation of the endogenous ABL kinases. To examine the consequences of depleting the ABL kinases on the transcriptome of metastatic breast cancer cells we employed next generation sequencing (RNAseq) analysis. We found that 180 genes were significantly down-regulated and 40 genes were significantly up-regulated in ABL1/ABL2 knockdown cells. Four samples were analyzed control, Abl single knockdown, Arg single knockdown, Abl/Arg double knockdown. Experiments were performed in triplicate.

2016-03-02 | E-GEOD-69125 | biostudies-arrayexpress

The effect of Abl kinases,or Ponatinib challenging on breast cancer cells' global transcriptome

Project description:To gain insight into the signaling pathway(s) required for ABL1/ABL2-kinase activity or effected by Ponatinib treatment, we evaluated the consequences of single or double inactivation of ABL1/ABL2 cells, or Ponatinib treated cells on the transcriptome of breast cancer cells. To examine the consequences of depleting the ABL kinases, or Ponatinib treatment on the transcriptome of lung metastatic breast cancer cells we employed next generation sequencing (RNAseq) analysis. We found that 321 genes were significantly differently expressed in Ponatinib treated LM2 cells, and 73 genes were differently expressed in double inactivation of ABL1/ABL2 LM2 cells. However, only about 3.4 percent of Ponatinib affected genes can also be changed by ABL knocking down.

2018-03-01 | GSE95079 | GEO

The role of ABL kinases in medulloblastoma

Project description:Medulloblastoma is the most common malignant pediatric brain tumor, and leptomeningeal dissemination (LMD) of medulloblastoma portends a poorer prognosis at diagnosis and is incurable at recurrence. The biological mechanisms underlying LMD in medulloblastoma are largely unclear. The Abelson (ABL) family of non-receptor tyrosine kinases has been implicated in cancer cell migration, invasion, adhesion, and chemotherapy resistance, and these kinases are upstream mediators of the oncogene c-MYC in fibroblasts. However, their role in medulloblastoma has not yet been explored. Therefore, the purpose of this work is to elucidate the role of the ABL kinases, ABL1 and ABL2, in medulloblastoma LMD. We show here that ABL1/2 mRNA is highly expressed in human medulloblastoma tumor samples and cell lines and that pharmacologic inhibition of ABL kinases results in medulloblastoma cell death. Knockdown of the ABL kinase genes ABL1 and ABL2 results in decreased adhesion to the extracellular matrix protein, vitronectin, and decreased medulloblastoma proliferation in a mouse model of medulloblastoma LMD (resulting in decreased tumor burden with subsequent increased overall survival. Further, both pharmacologic inhibition of ABL1/2 and ABL1/2 knockdown resulted in decreased c-myc expression, revealing a putative signaling pathway. In summary, this work highlights the potential role of ABL kinases in medulloblastoma LMD via c-myc expression.

2023-10-04 | GSE224691 | GEO

Abl subtrates using tyrosine phosphoproteomics

Project description:In this study, we have prepared a mouse embryonic fibrobalst (MEF) cell line stably expressing R367A mutant human Abl in which the native mouse Abl1 and Abl2 were genetically deleted. We have used these R367A mutant Abl cells in combination with mass spectrometry to identify phosphorylation targets of Abl. Below, we describe these findings and their potential biological significance.

2018-03-16 | PXD007118 | Pride

Identification of phosphorylation sites on Abl2

Project description:The catalytic activity of Abl family kinases is tightly regulated in cells by a complex set of intra- and intermolecular interactions and post-translational modifications. Abl family kinases are activated by diverse cellular stimuli, one of them being receptor tyrosine kinase signaling. For example, platelet-derived growth factor receptor beta (PDGFRβ) has been identified as a potent activator of Abl family kinases. However, the molecular mechanism by which PDGFRβ engages and activates Abl family kinases is not known. We report here the molecular mechanism by which PDGFRβ interacts, phosphorylates and activates Abl2 kinase. We found that PDGFRβ binds and phosphorylates Abl2 both in vitro and in cells. We also identified several novel PDGFRβ phosphorylation sites on Abl2, including Y116, Y139 and Y161 on the SH3 domain, and Y299, Y303 and Y310 on the kinase domain. Of notable interest, Y116, Y161, Y272 and Y310 are all located near the SH3/SH2-kinase linker interface, which help maintain Abl family kinases in an auto-inhibited conformation. Mutation of these four tyrosine (Y116, Y161, Y272 and Y310) to phenylalanine abrogated PDGFRβ-mediated activation of Abl2 kinase activity. These findings provide a mechanism to understand how receptor tyrosine kinases activate Abl family kinases, and how Abl kinases are precisely regulated through different phosphorylation events.

2022-02-17 | PXD025896 | Pride

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Project description:Analysis of changes in the phosphoproteome upon transient siRNA-mediated knockdown of ABL1/ABL2 or DDR1 for 48 hours. CILAC phosphoproteome analysis was conducted after 48hrs using human U-2 OS cells.

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Project description:Extracellular perception of auxin, an essential phytohormone in plants, has been debated for decades. Auxin binding protein 1 (ABP1) physically interacts with quintessential transmembrane kinases (TMKs) and was proposed to act as an extracellular auxin receptor, but its role was disputed because abp1 knockout mutants lack obvious morphological phenotypes. Here we identified two new auxin-binding proteins, ABL1 and ABL2, that are localized to the apoplast and directly interact with the extracellular domain of TMKs in an auxin-dependent manner. Furthermore, functionally redundant ABL1 and ABL2 genetically interact with TMKs and exhibit functions that are overlapping with those of ABP1 as well as independent of ABP1. Importantly, the extracellular domain of TMK1 itself binds auxin and synergizes with either ABP1 or ABL1 in auxin binding. Thus, our findings discovered new auxin receptors ABL1 and ABL2 having functions overlapping with but distinct from ABP1 and acting together with TMKs as co-receptors for extracellular auxin.

2023-11-25 | PXD044623 | Pride

Homo sapiens

Project description:The effect of knockdown Abl kinases on breast cancer cells' global transcriptome

| PRJNA284608 | ENA

Bulk RNA-seq was performed on murine Lin-Sca+Kit+ (LSK) bone marrow cells from a transgenic SCLtTA/BCR-ABL (DTG) mouse BM cells (CD45.2) in which BCR-ABL1 was expressed or not expressed

Project description:Bulk RNA-seq was performed on murine Lin-Sca+Kit+ bone marrow cells from a transgenic SCLtTA/BCR-ABL (DTG) mouse BM cells (CD45.2) to understand the molecular consequences of BCR-ABL1 expression on the global mRNA programme of these cells.

2023-12-19 | GSE242036 | GEO

The effect of Abl kinases on non-small cell carcinoma global transcriptome

Project description:To gain insight into the signaling pathway(s) required for ABL1/ABL2-dependent non-small cell carcinoma cells metastasis

2017-01-28 | GSE77422 | GEO