Integrin-linked kinase (ILK) regulates KRAS, IPP complex and Ras suppressor-1 (RSU1) promoting lung adenocarcinoma progression and poor survival

Nikou, Sofia; Arbi, Marina; Dimitrakopoulos, Foteinos-Ioannis; Sirinian, Chaido; Chadla, Panagiota; Pappa, Ioanna; Ntaliarda, Giannoula; Stathopoulos, Georgios T.; Papadaki, Helen; Zolota, Vasiliki; Lygerou, Zoi; Kalofonos, Haralabos; Bravou, Vasiliki

doi:10.1007/s10735-020-09888-3

Cited by 16 publications

(16 citation statements)

References 61 publications

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“…ILK is conceptually a multifunctional intracellular effector of cell-matrix interaction, which can directly interact with β1 or β3 integrin subunit; ILK can coordinate various signal pathways, modulate cell proliferation by activating Akt signaling, and directly act on GSK-3β to activate some transcription factors [ 8 ]. In lung adenocarcinoma, as reported, ILK can regulate KRAS, IPP complex and Ras suppressor-1 (RSU1) to promote cancer cell multiplication, migration and epithelial-mesenchymal transition (EMT), and its high expression is pertinent to poor prognosis [ 21 ]. In glioma, ILK promotes cancer cell migration and aggressiveness via activating ROCK1 and fascin-1 [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circ_0000515 adsorbs miR-542-3p to accelerate bladder cancer progression via up-regulating ILK expression

Peng

Guan²,

Leng

et al. 2022

Aging

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Background: Bladder cancer (BC) is a common cause of cancer-relevant deaths globally. This study is designed to delve into expressions, biological functions and molecular mechanisms of circ_0000515 in BC. Methods: Quantitative real-time polymerase chain reaction was accomplished to examine circ_0000515, miR-542-3p and integrin-linked kinase (ILK) mRNA expressions in BC tissues and cell lines. In RT-4 and RT-112 cells with circ_0000515 depletion and UMUC3 and BIU-87 cells with this circ RNA overexpression, a cell counting kit-8 assay was adopted to monitor the viability. Besides, transwell assay was conducted to detect cell migration and aggressiveness, and luciferase reporter gene assay was applied to probe the interplay among circ_0000515, miR-542-3p and ILK mRNA. Additionally, Besides, the regulatory function of circ_0000515 on miR-542-3p expression was under the assay of quantitative real-time polymerase chain reaction, and western blot was fulfilled to determine the regulative function of circ_0000515/miR-542-3p axis on ILK protein expressions. A xenograft animal was modeled to examine lung metastasis in vivo . Results: Circ_0000515 and ILK expressions were significantly elevated in BC tissues and cell lines, while that of miR-542-3p was dramatically suppressed. Knocking down circ_0000515 could significantly repress the growth, migration and aggressiveness of BC cells while overexpression of circ_0000515 showed opposite effects. Moreover, circ_0000515 knockdown inhibited pulmonary metastasis in vivo . Circ_0000515 was validated to adsorb miR-542-3p, and ILK was testified as the downriver target of miR-542-3p. Circ_0000515 could ascend ILK expression through repressing that of miR-542-3p. Conclusions: Circ_0000515, as a tumor promoter, strengthens the viability, migration and aggressiveness of BC cells via modulating miR-542-3p/ILK axis.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circ_0000515 adsorbs miR-542-3p to accelerate bladder cancer progression via up-regulating ILK expression

Peng

Guan²,

Leng

et al. 2022

Aging

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“…In recent years, ILK has been reported as being involved in the drug-sensitivity of many types of tumors. For example, ILK could regulate the sensitivity of pancreatic cancer cells to gemcitabine [ 16 ], and the pharmacological inhibition of ILK in oncogene homolog (KRAS) mutant lung cancer cells could inhibit cell growth, migration, and epithelial mesenchymal transition, and increase sensitivity to CDDP chemotherapy [ 30 ]. These results suggested that ILK played an important role in the regulation of tumor sensitivity to chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Integrin-linked kinase affects the sensitivity of esophageal squamous cell carcinoma cells to chemotherapy with cisplatin via the Wnt/beta-catenin signaling pathway

et al. 2022

Bioengineered

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Recent studies have shown that the expression of integrin-linked kinase (ILK) was related to the occurrence, development, and malignant progression of esophageal squamous cell carcinoma (ESCC). However, research on the relationship between ILK and the chemosensitivity of ESCC has to date not been reported. The present study found that ILK was highly expressed in ESCC cell lines, and the overexpression of ILK in ESCC cells reduced the incidence of cell apoptosis and alleviated the cytotoxicity on cells induced by cisplatin (CDDP). Inversely, ILK knockdown increased CDDP-induced apoptosis and had an inhibitive effect on the malignant phenotype of ESCC, including cell proliferation, invasion, and migration. In addition, ILK knockdown in ESCC cells inhibited the expression of beta (β)-catenin and activated the wingless/integrated (Wnt) signaling pathway. Furthermore, cellular MYC (c-MYC) and Cylin D1 were the target genes of the Wnt signaling pathway. Rescue experiments showed that the overexpression of β-catenin reversed a tumor’s inhibition and apoptosis abilities induced by ILK knockdown. In conclusion, ILK potentially reduced the CDDP sensitivity of ESCC cells by influencing the activity of the Wnt/β-catenin signaling pathway.

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“…The ILK pathway has been associated with migration, invasion, EMT, cancer stem cell marker and chemotherapy resistance in CRC [ 45 , 71 ]. Furthermore, the ILK pathway was found to cross-talk with the KRAS pathway via a KRAS-ILK-hnRNPA1 regulatory loop in pancreatic cancer [ 72 ] as well as in lung adenocarcinoma [ 73 ]. In prostate cancer, KRAS regulates ILK expression mediated by E2F1 in a KRAS-E2F1-ILK-hnRNP1 loop [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Common and mutation specific phenotypes of KRAS and BRAF mutations in colorectal cancer cells revealed by integrative -omics analysis

Kundu

Akhtar-Ali

Handin

et al. 2021

J Exp Clin Cancer Res

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Background Genes in the Ras pathway have somatic mutations in at least 60 % of colorectal cancers. Despite activating the same pathway, the BRAF V600E mutation and the prevalent mutations in codon 12 and 13 of KRAS have all been linked to different clinical outcomes, but the molecular mechanisms behind these differences largely remain to be clarified. Methods To characterize the similarities and differences between common activating KRAS mutations and between KRAS and BRAF mutations, we used genome editing to engineer KRAS G12C/D/V and G13D mutations in colorectal cancer cells that had their mutant BRAF V600E allele removed and subjected them to transcriptome sequencing, global proteomics and metabolomics analyses. Results By intersecting differentially expressed genes, proteins and metabolites, we uncovered (i) two-fold more regulated genes and proteins when comparing KRAS to BRAF mutant cells to those lacking Ras pathway mutation, (ii) five differentially expressed proteins in KRAS mutants compared to cells lacking Ras pathway mutation (IFI16, S100A10, CD44, GLRX and AHNAK2) and 6 (CRABP2, FLNA, NXN, LCP1, S100A10 and S100A2) compared to BRAF mutant cells, (iii) 19 proteins expressed differentially in a KRAS mutation specific manner versus BRAF V600E cells, (iv) regulation of the Integrin Linked Kinase pathway by KRAS but not BRAF mutation, (v) regulation of amino acid metabolism, particularly of the tyrosine, histidine, arginine and proline pathways, the urea cycle and purine metabolism by Ras pathway mutations, (vi) increased free carnitine in KRAS and BRAF mutant RKO cells. Conclusions This comprehensive integrative -omics analysis confirms known and adds novel genes, proteins and metabolic pathways regulated by mutant KRAS and BRAF signaling in colorectal cancer. The results from the new model systems presented here can inform future development of diagnostic and therapeutic approaches targeting tumors with KRAS and BRAF mutations.

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Integrin-linked kinase (ILK) regulates KRAS, IPP complex and Ras suppressor-1 (RSU1) promoting lung adenocarcinoma progression and poor survival

Cited by 16 publications

References 61 publications

Circular RNA circ_0000515 adsorbs miR-542-3p to accelerate bladder cancer progression via up-regulating ILK expression

Circular RNA circ_0000515 adsorbs miR-542-3p to accelerate bladder cancer progression via up-regulating ILK expression

Integrin-linked kinase affects the sensitivity of esophageal squamous cell carcinoma cells to chemotherapy with cisplatin via the Wnt/beta-catenin signaling pathway

Common and mutation specific phenotypes of KRAS and BRAF mutations in colorectal cancer cells revealed by integrative -omics analysis

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