Transforming growth factor-beta signaling in normal and malignant hematopoiesis.
Transforming growth factor-beta (TGF-beta) is an important physiologic regulator of cell growth and differentiation. TGF-beta has been shown to inhibit the proliferation of quiescent hematopoietic stem cells and stimulate the differentiation of late progenitors to erythroid and myeloid cells. Insensitivity to TGF-beta is implicated in the pathogenesis of many myeloid and lymphoid neoplasms. Loss of extracellular TGF receptors and disruption of intracellular TGF-beta signaling by oncogenes is seen in a variety of malignant and premalignant states. TGF-beta can also affect tumor growth and survival by influencing the secretion of other growth factors and manipulation of the tumor microenvironment. Recent development of small molecule inhibitors of TGF-beta receptors and other signaling intermediaries may allow us to modulate TGF signaling for future therapeutic interventions in cancer.
Isufi
Iris
I
Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Seetharam
Mahesh
M
Zhou
Li
L
Sohal
Davendra
D
Opalinska
Joanna
J
Pahanish
Perry
P
Verma
Amit
A
D000818:Animals; D017209:Apoptosis; D006410:Hematopoiesis; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008223:Lymphoma / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta