title: DOC-2/hDab-2 inhibits ILK activity and induces anoikis in breast cancer cells through an Akt-independent pathway.
abstract: DOC-2/hDab-2 was identified due to the loss of its expression in primary ovarian cancer cells. It is believed that loss of DOC-2/hDab-2 expression is one of the early events of ovarian malignancy. These results suggest a function of DOC-2/hDab-2 as a tumor suppressor. However, it is not clear how DOC-2/hDab-2 negatively regulates cancer cell growth. In this report, we demonstrate that DOC-2/hDab-2 expression in breast cancer cells resulted in sensitivity to suspension-induced cell death (anoikis). This event was associated with the down-regulation of the integrin-linked kinase (ILK) activity. Since ILK is a key factor in regulating the cellular signaling in responding to the extracellular signals through adhesion molecules like integrins, our results indicate that DOC-2/hDab-2 may prevent tumor growth and invasion by modulating the anti-apoptotic ILK pathway.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Makino
authors.forename: W
authors.initials: W
authors.lastname: Xia
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.forename: S A
authors.initials: SA
authors.lastname: Im
authors.forename: H
authors.initials: H
authors.lastname: Peng
authors.forename: S C
authors.initials: SC
authors.lastname: Mok
authors.forename: S E
authors.initials: SE
authors.lastname: Singletary
authors.forename: M C
authors.initials: MC
authors.lastname: Hung
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000256:Adenoviridae / Q000235:genetics; D023102:Anoikis; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016147:Genes, Tumor Suppressor; D005822:Genetic Vectors; D006801:Humans; D020935:MAP Kinase Signaling System; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D000099200:Scaffold Protein ILK
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D025521:Tumor Suppressor Proteins; D000099200:Scaffold Protein ILK; C102885:DAB2 protein, human; C494918:AKT1 protein, human