Department of Chemical Biology
Center for Cancer Prevention Research
RBHS, Ernest Mario School of Pharmacy
Cancer Institute of New Jersey
Ph.D., 1992, Harvard University
Telephone: (848) 445-9783
Fax: (732) 235-4850
TGF-β signal transduction, transcriptional regulation, cell cycle control, cancer
Transforming growth factor-β (TGF-β) and related polypeptides, including activins and bone morphogenetic proteins (BMPs), constitute the largest cytokine family, possessing fascinating features. They are multifunctional, regulating essentially all aspects of cellular processes. For example, TGF-β potently inhibits cell proliferation by causing cell cycle arrest at the G1 phase. Accordingly, TGF-β is a potent tumor suppressor at early stages of tumorigenesis. TGF-β also regulates cell differentiation, adhesion, motility and apoptosis. TGF-β family members are evolutionarily conserved and play an essential role in the development and homeostasis of virtually every tissue in organisms ranging from fruit flies to humans. Inactivating mutations in several components of the TGF-β signaling pathways have been found in human disorders, such as cancer.
TGF-β signals through transmembrane serine/threonine kinase receptors. It binds and brings together two classes of receptors, the type I and type II receptors. The TGF-β type II receptor is constitutively active. It transphosphorylates the type I receptor, which then plays a major role in specifying downstream events, leading to various biological responses.
Smad proteins transduce the TGF-β signal from the cell surface to the nucleus. Smads are directly phosphorylated by the TGF-β family receptor kinases upon ligand stimulation. Following phosphorylation, Smads form heteromeric complexes, accumulate in the nucleus, and regulate transcription of a variety of target genes, such as cell cycle regulators.
Our current research is focused on the TGF-β/Smad signal transduction, transcriptional regulation, cell cycle control, and their roles in cancer, in particular breast cancer.
Liu Z, Kundu-Roy T, Matsuura I, Wang G, Lin Y, Lou YR, Barnard NJ, Wang XF, Huang MT, Suh N, Liu F. (2016) Carcinogen 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis is accelerated in smad3 heterozygous mice compared to Smad3 wild type mice. Oncotarget 7:64878-85
Liu F, Matsuura I. (2016) Phosphorylation of Smads by intracellular kinases. Methods Mol Biol 1344:93-109
Andrade D, Velinder M, Singer J, Maese L, Bareyan D, Nguyen H, Chandrasekharan MB, Lucente H, McClellan D, Jones D, Sharma S, Liu F, Engel ME. (2016) SUMOylation regulates growth factor independence 1 in transcriptional control and hematopoiesis. Mol Cell Biol 36:1438-50
Bae E, Sato M, Kim RJ, Kwak MK, Naka K, Gim J, Kadota M, Tang B, Flanders KC, Kim TA, Leem SH, Park T, Liu F, Wakefield LM, Kim SJ, Ooshima A. (2014) Definition of Smad3 phosphorylation events that affect malignant and metastatic behaviors in breast cancer cells. Cancer Res 74:6139-49
So JY, Smolarek AK, Salerno DM, Maehr H, Uskokovic M, Liu F, Suh N. (2013) Targeting CD44-STAT3 signaling by Gemini vitamin D analog leads to inhibition of invasion in basal-like breast cancer. PLoS ONE 8:e54020
So JY, Lee HJ, Smolarek AK, Paul S, Wang CX, Maehr H, Uskokovic M, Zheng X, Conney AH, Cai L, Liu F, Suh N. (2011) A novel Gemini vitamin D analog represses the expression of a stem cell marker CD44 in breast cancer. Mol Pharmacol 79:360-7
Liu F. (2011) Inhibition of Smad3 activity by cyclin D-CDK4 and cyclin E-CDK2 in breast cancer cells. Cell Cycle 10:186
Matsuura I, Chiang KN, Lai CY, He D, Wang G, Ramkumar R, Uchida T, Ryo A, Lu K, Liu F. (2010) Pin1 promotes transforming growth factor-β-induced migration and invasion. J Biol Chem 285:1754-64
Wang G, Matsuura I, He D, Liu F. (2009) Transforming growth factor-β-inducible phosphorylation of Smad3. J Biol Chem 284:9663-73
Wang G, Long J, Matsuura I, He D, Liu F. (2005) The Smad3 linker region contains a transcriptional activation domain. Biochem J 386:29-34
Matsuura I, Wang G, He D, Liu F. (2005) Identification and characterization of ERK MAP kinase phosphorylation sites in Smad3. Biochemistry 44:12546-53
Matsuura I, Denissova NG, Wang G, He D, Long J, Liu F. (2004) Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature 430:226-31