Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disruption of integrin-extracellular matrix interactions in normal epithelial cells induces apoptosis, a process termed anoikis. Reduced sensitivity to anoikis appears to be an important hallmark of oncogenic transformation, particularly in the process of metastasis. Several pathways have been implicated in the suppression of anoikis, however, the events which take place proximal to the integrin receptors remain unclear. Integrin-linked kinase (ILK) is an integrin-interacting protein kinase which has been identified as a potential PDK-2, as it is capable of phosphorylating PKB/Akt on Ser-473, and stimulating its activity. Here, we show that ILK activity is stimulated upon adhesion of SCP2 mouse mammary epithelial cells to fibronectin, and inhibited in suspended cells. Overexpression of ILK in the anoikis-sensitive SCP2 cells results in a profound inhibition of anoikis, as determined by annexin V binding and activation of caspases 8 and 3. This effect is reversible by the transfection and expression of a dominant-negative, kinase deficient ILK (ILK KD), as well as by a dominant negative PKB/Akt (PKB AAA). On the other hand, transfection of a dominant negative form of FAK (FRNK) failed to reverse the suppression of anoikis by ILK. Furthermore, inhibition of ILK activity induced anoikis in two anoikis-resistant human breast cancer cell lines. These findings suggest that ILK plays a major role in the suppression of anoikis.
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PMID:The integrin-linked kinase (ILK) suppresses anoikis. 1094 37

Abdominal aortic aneurysm (AAA) is a progressive chronic dilatation of the abdominal aorta without effective medical treatment. This study aims to clarify the potential of long non-coding RNA SENCR as a treatment target in AAA. Angiotensin II (Ang-II) was used to establish AAA mouse model as well as a cell model based on the mouse aortic vascular smooth muscle cells (VSMCs). Reverse transcription quantitative PCR and western blot were performed to measure the expression of SENCR and proteins, respectively. Apoptotic rate in VSMCs was determined using Annexin V-FITC/PI double staining, and cell apoptosis in aortic tissues was determined by TUNEL staining. Hematoxylin and eosin and Elastica van Gieson staining were used for histological analysis of aortic tissues. SENCR was downregulated in AAA tissues and Ang-II-stimulated VSMCs. Overexpression of SENCR inhibited Ang-II-induced VSMC apoptosis, while inhibition of SENCR facilitated VSMC apoptosis. Moreover, overexpression of SENCR suppressed matrix metalloproteinase (MMP)-2 and MMP-9 expression and promoted tissue inhibitor of metalloproteinases 1 (TIMP-1) expression in Ang-II-induced VSMCs, while inhibition of SENCR expression led to the opposite results. In vivo, overexpressed SENCR improved the pathological change in aortic tissues and the damage in arterial wall elastic fibres induced by Ang-II, as well as it suppressed Ang-II-induced cell apoptosis and extracellular matrix degradation in aortic tissues. Overall, overexpression of SENCR inhibited AAA formation via suppressing VSMC apoptosis and extracellular matrix degradation. We provided a reliable evidence for SENCR acting as a potential target for AAA treatment.
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PMID:LncRNA SENCR suppresses abdominal aortic aneurysm formation by inhibiting smooth muscle cells apoptosis and extracellular matrix degradation. 3290 73