Integrin-Linked Kinase (ILK) Expression Correlates with Tumor Severity in Clear Cell Renal Carcinoma

Engelman, Miriam de Fátima Brasil; Grande, Rogério Mendes; Naves, Marcelo Andery; Franco, Marcello; Teixeira, Vicente de Paulo Castro

doi:10.1007/s12253-012-9554-4

Cited by 18 publications

(14 citation statements)

References 37 publications

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“…A recent study suggested a possible role for ILK in the progression of RCC by showing that ILK expression is correlated with tumor severity in clear-cell RCC (29). In this study, the RCC cell line from a metastatic lesion showed the highest expression of ILK and displayed higher expression of EMT-related transcriptional factors Snail and Zeb1, which suggests that ILK might be related to the metastatic potential of RCC cells.…”

Section: Discussionsupporting

confidence: 58%

Targeting Integrin-Linked Kinase Suppresses Invasion and Metastasis through Downregulation of Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma

Han

Raven

et al. 2015

Molecular Cancer Therapeutics

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Renal cell carcinoma (RCC) is the most common malignancy in the kidney. Antiangiogenic targeted therapies inhibit the progression of RCC, but have limited impacts on invasion or metastasis of tumor cells. Integrin-linked kinase (ILK) is a serine/threonine kinase implicated in the regulation of cell growth/survival, cellcycle progression, epithelial-mesenchymal transition (EMT), invasion/migration, and angiogenesis. However, the role of ILK in RCC has not been evaluated. We investigated the role of ILK on cancer progression and metastasis and the therapeutic potential of ILK inhibition in RCC. Our investigation reveals that ILK is expressed at a low level in normal cells and low-stage RCC cells and is highly expressed in advanced and metastatic cells. Caki-1, a metastatic RCC cell line, showed higher expression of molecular EMT markers, including Snail and Zeb1, but decreased activity of GSK3b. Knockdown of ILK using small interference (si)-ILK minimally inhibited tumor proliferation and cell-cycle progression was not significantly affected. However, ILK knockdown suppressed the formation of stress fibers and focal adhesions and impeded phenotypic EMT markers, including cell migration and invasion, in Caki-1 and UMRC-3 cells. Finally, in vivo knockdown of ILK suppressed the progression, invasion, and metastasis of primary RCC in nude mice by downregulation of EMT markers (Snail, Zeb1, vimentin,. Our results show that ILK may be essential for invasion and metastasis in RCC and regulates vimentin and E-cadherin expression by regulating the EMT-related transcription factors Snail and Zeb1. These results suggest that ILK may be a potential target in RCC.

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Section: Discussionsupporting

confidence: 58%

Targeting Integrin-Linked Kinase Suppresses Invasion and Metastasis through Downregulation of Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma

Han

Raven

et al. 2015

Molecular Cancer Therapeutics

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“…Knockdown of ILK was shown to inhibit cell migration and invasion in the Caki-1 cell line and downregulation of epithelial-mesenchymal transition (EMT) markers in an in vivo study (34). Another recent study showed that in ccRCC patients, ILK expression was significantly increased in high-grade tumors compared with low-grade tumors (17). Furthermore, tumors with positive ILK expression showed a higher proliferation index than tumors with negative ILK expression.…”

Section: Discussionmentioning

confidence: 97%

Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line

Khan

Dębski

Dąbrowski

et al. 2016

American Journal of Physiology-Renal Physiology

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“…Renal cell carcinoma (RCC) is the most common kidney cancer and represents approximately 3% of all adult malignancies [1][2][3]. There has been an increase in the incidence of RCC in recent years.…”

Section: Introductionmentioning

confidence: 99%

Renin-angiotensin system (RAS) blockade attenuates growth and metastatic potential of renal cell carcinoma in mice

Araújo¹,

Naves²,

Ravanini³

et al. 2015

Urologic Oncology: Seminars and Original Investigations

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Integrin-Linked Kinase (ILK) Expression Correlates with Tumor Severity in Clear Cell Renal Carcinoma

Cited by 18 publications

References 37 publications

Targeting Integrin-Linked Kinase Suppresses Invasion and Metastasis through Downregulation of Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma

Targeting Integrin-Linked Kinase Suppresses Invasion and Metastasis through Downregulation of Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma

Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line

Renin-angiotensin system (RAS) blockade attenuates growth and metastatic potential of renal cell carcinoma in mice

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