Deregulated TGF-beta signaling in leukemogenesis.
Cellular homeostasis is tightly controlled by the various pathways that regulate cell proliferation and cell death. Breaking this balance is often associated with cancer development. The transforming growth factor-beta (TGF-beta) pathway plays an important role in cellular homeostasis by regulating cell growth inhibition, cellular senescence, differentiation and apoptosis. Deregulated TGF-beta signaling is known to be involved in a variety of human cancers, including those of the colon, pancreas, breast and prostate. While TGF-beta is a potent negative regulator of hematopoiesis, the role of aberrant TGF-beta signaling in leukemogenesis remains largely unknown. Recently, evidence demonstrating deregulated TGF-beta signaling in leukemogenesis, particularly in acute promyelocytic leukemia (APL), has started to emerge. In this review, we summarize the current progress towards the understanding of the molecular mechanisms by which aberrant TGF-beta signaling may participate in leukemogenesis.
Lin
Hui-Kuan
HK
Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.
Bergmann
Stephan
S
Pandolfi
Pier Paolo
PP
D011992:Endosomes / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000209:etiology*; D015473:Leukemia, Promyelocytic, Acute / Q000209:etiology; D021962:Membrane Microdomains / Q000502:physiology; D009363:Neoplasm Proteins / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology; D000071156:Promyelocytic Leukemia Protein; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; C070576:PML protein, human