Integrin-Linked Kinase (ILK) Expression as a Biomarker in Cancer of the Kidney

Abstract

Integrin-linked kinase (ILK) is a serine/threonine protein kinase implicated in cell-cycle control via integration of integrins with the extracellular matrix. Integrin-linked kinase overexpression promotes anchorage-independent growth and may induce tumorigenesis and invasion. Integrin-linked kinase suppresses anoikis, suggesting that it has a role in oncogenic transformation, particularly in the process of metastasis. Due to its effects on the cell cycle, apoptosis, cell adherence, and in the breakdown of collagen and cellularmobility, integrin-linked kinase has been the subject of numerous studies, particularly in the field of oncology. ILK expression and activity are increased in several human cancers, including prostate, colon, stomach, ovary, malignant melanomas, Ewing's sarcoma, primitive neuroectodermal tumor, non-small-cell lung cancer, bladder cell carcinoma, basal cell carcinoma, squamous cell/adenosquamous carcinomas, adenocarcinoma of the gallbladder, malignant pleural mesothelioma, chondrosarcoma, and pancreatic cancer. Renal cell carcinoma is a tumor derived from epithelial cells of the renal tubules and represents 80-85 % of all primary malignant tumors of the kidney and 2-3 % of all cancers in adults. Among renal cell carcinomas, clear renal cell carcinomas are the most frequent, accounting for 70-80 % of cases. These neoplasms may be family associated or, in the majority of cases (95 %), sporadic. Both types are related to loss of function of the VHL gene, which acts as a tumor suppressor. Clear renal cell carcinomas at identical stages and pathological grades may exhibit distinct biological behavior, and consequently prognosis markers are urgently needed. In clear renal cell carcinoma, integrin-linked kinase immunoexpression is related to loss of intercellular adhesion and degree of differentiation, and it is positively correlated with the proliferation index, renal capsule and renal vein invasion, tumor size, and Robson stage. Integrin-linked kinase may be essential for invasion and metastasis in renal cell carcinoma. Integrin-linked kinase may also act through the phosphoinositide 3-kinase (PI3K)-Akt pathway to promote cell survival in human renal cell carcinoma. Integrin-linked kinase may act as a phosphoinositide-dependent kinase (PDK)-2 by facilitating Akt phosphorylation at S473. Altogether, results reviewed here indicate that the PI3K/ILK/Akt axis is a promising target for therapeutic intervention in renal cell carcinoma and that integrin-linked kinase expression might be used in clinical practice as an important predictive and prognostic tumor marker for treatment customization.