Oncogenic ILK, tumor suppression and all that JNK.
In neoplastic cells, proteins exert either pro or anti-tumorigenic functions. However, some proteins exhibit both properties, commonly dependent on specific aberrations occurring in a tumor-specific context. Recently, we demonstrated that the integrin-linked kinase (ILK), generally characterized as an oncogenic protein kinase, functions as a tumor suppressor protein in vitro and in vivo in the aggressive pediatric tumor, rhabdomyosarcoma (RMS). Other studies have similarly demonstrated both growth and tumor suppressive functions for ILK in normal and transformed tissues. The mechanism of ILK tumor suppression in RMS relies on expression levels of another kinase, the c-jun amino terminal kinase-1 (JNK1). These findings support a model in which ILK tumor suppression is mediated in part by elevated JNK1 expression, and indicate both a rationale for stratification of patients to receive anti-ILK therapies, and a need to better understand the context in which ILK displays its seemingly contradictory functions. This review discusses the complex roles of ILK in tumorigenesis, and offers arguments to harness ILK and JNK signaling as novel targets for anti-cancer therapy.
Durbin
Adam David
AD
Department of Medical Biophysics, University of Toronto, Toronto, ON, CA.
Hannigan
Gregory Edward
GE
Malkin
David
D
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000099200:Scaffold Protein ILK
D048031:JNK Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; D000099200:Scaffold Protein ILK