Integrin-Linked-Kinase Overexpression Is Implicated in Mechanisms of Genomic Instability in Human Colorectal Cancer

Chadla, Panagiota; Arbi, Marina; Nikou, Sofia; Καλλιακούδας, Θεόδωρος; Papadaki, Helen; Taraviras, Stavros; Lygerou, Zoi; Bravou, Vasiliki

doi:10.1007/s10620-020-06364-6

Cited by 7 publications

(2 citation statements)

References 44 publications

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“…Although discussing ILKs action regulation, it is crucial to acknowledge the existence of an ILK inhibitor, QLT267, also known as QLT-267 or QLT0267, which is commercially available. Several studies are employing this compound [99][100][101][102][103][104]. However, caution should be taken while using this inhibitor as it has never been unambiguously characterized in literature, whether it directly binds to ILK or is specific.…”

Section: Ilk Is Most Probably a Pseudokinasementioning

confidence: 99%

Integrin-linked kinase (ILK): the known vs. the unknown and perspectives

Górska

Mazur

2022

Cell. Mol. Life Sci.

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Integrin-linked kinase (ILK) is a multifunctional molecular actor in cell–matrix interactions, cell adhesion, and anchorage-dependent cell growth. It combines functions of a signal transductor and a scaffold protein through its interaction with integrins, then facilitating further protein recruitment within the ILK–PINCH–Parvin complex. ILK is involved in crucial cellular processes including proliferation, survival, differentiation, migration, invasion, and angiogenesis, which reflects on systemic changes in the kidney, heart, muscle, skin, and vascular system, also during the embryonal development. Dysfunction of ILK underlies the pathogenesis of various diseases, including the pro-oncogenic activity in tumorigenesis. ILK localizes mostly to the cell membrane and remains an important component of focal adhesion. We do know much about ILK but a lot still remains either uncovered or unclear. Although it was initially classified as a serine/threonine-protein kinase, its catalytical activity is now questioned due to structural and functional issues, leaving the exact molecular mechanism of signal transduction by ILK unsolved. While it is known that the three isoforms of ILK vary in length, the presence of crucial domains, and modification sites, most of the research tends to focus on the main isoform of this protein while the issue of functional differences of ILK2 and ILK3 still awaits clarification. The activity of ILK is regulated on the transcriptional, protein, and post-transcriptional levels. The crucial role of phosphorylation and ubiquitylation has been investigated, but the functions of the vast majority of modifications are still unknown. In the light of all those open issues, here we present an extensive literature survey covering a wide spectrum of latest findings as well as a past-to-present view on controversies regarding ILK, finishing with pointing out some open questions to be resolved by further research.

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Section: Ilk Is Most Probably a Pseudokinasementioning

confidence: 99%

Integrin-linked kinase (ILK): the known vs. the unknown and perspectives

Górska

Mazur

2022

Cell. Mol. Life Sci.

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“…In CRC, overexpression of ILK is associated with genomic instability, epithelial-mesenchymal transition (EMT), and cancer stem cells (CSCs) traits, which contribute to tumor progression, migration, invasion, and chemoresistance via NF-κB, CTEN signals, etc. [10][11][12][13][14][15]. High immunohistochemical expression of ILK is associated with poor prognostic and pathological parameters [15,16].…”

Section: Introductionmentioning

confidence: 99%

Silencing LncRNA CASC9 inhibits proliferation and invasion of colorectal cancer cells by MiR-542-3p/ILK

Zhang

Wang

et al. 2022

PLoS ONE

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Colorectal cancer (CRC) ranks the third in cancers and the second in the reasons of cancer-related death. More evidence indicates that long non-coding RNA participates in tumor initiation and progression. It’s known that cancer susceptibility candidate 9 is an oncogenic long non-coding RNA in CRC. miR-542-3p is a negative regulator of CRC, while integrin-linked kinase could contribute to tumor progression and chemoresistance. However, the correlation among long non-coding RNA cancer susceptibility candidate 9, miR-542-3p and integrin-linked kinase in CRC is still unclear. We demonstrated long non-coding RNA cancer susceptibility candidate 9 in CRC specimens and cell lines overexpressed via real-time quantitative polymerase chain reaction. Once long non-coding RNA cancer susceptibility candidate 9 was knocked down, it significantly inhibited proliferation, invasion, and migration of CRC cells in real-time quantitative polymerase chain reaction, cell counting kit-8, 5-ethynyl-2’-deoxyuridine, and transwell assays, which also was validated in vivo. Long non-coding RNA cancer susceptibility candidate 9 negatively regulates miR-542-3p in a targeted manner, and the function of up-regulated miR-542-3p was confirmed similarly. While miR-542-3p negatively regulates integrin-linked kinase. Thus, we further verified that overexpression of integrin-linked kinase on down-regulated long non-coding RNA cancer susceptibility candidate 9 or up-regulated miR-542-3p significantly restored CRC cell proliferation via bioinformatic analysis, dual-luciferase report assay, real-time quantitative polymerase chain reaction, RNA immunoprecipitation, and western blot. This study testified that silencing long non-coding RNA cancer susceptibility candidate 9 could inhibit proliferation and invasion of CRC cells by miR-542-3p/integrin-linked kinase.

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