University of Medicine and Dentistry of New Jersey

Pahujaa M, Anikin M, Goldberg GS Phosphorylation of connexin43 induced by Src: Regulation of gap junctional communication between transformed cells. . Exp Cell Res.. Vol. Sep 20;: (2007 ) .

Shen Y, Khusial PR, Li X, Ichikawa H, Moreno AP, Goldberg GS SRC utilizes Cas to block gap junctional communication mediated by connexin43. . J Biol Chem. Vol. Jun 29;282(26): 18914-21 (2007 ) .

Patwardhan P, Shen Y, Goldberg GS, Miller WT Individual Cas phosphorylation sites are dispensable for processsive phosphorylation by SRC and anchorage-independent cell growth. J Biol Chem. Vol. 2006 Jul; 281(30): 20689-20697 (2006 ) .

Shen Y, Jia Z, Nagele RG, Ichikawa H, Goldberg GS SRC uses Cas to suppress Fhl1 in order to promote nonanchored growth and migration of tumor cells. Cancer Res. Vol. 2006 Feb 1;66(3): 1543-52 (2006 ) .

Naus, C.C., Goldberg, G.S. and Sin, W.C. Connexins in growth control and cancer.. In: Winterhager, E. (Eds.) Gap junctions in development and disease. . Vol. New York: Spinger-Verlag: Pp. 253-265. (2005 ) .

Goldberg GS, Kunimoto, T., Alexander, D.B., Suenaga, K., Ishidate, F., Miyamoto, K., Ushijima, T., Teng, C.T., Yokota, J., Ohta, T., Tsuda, H Full length and delta lactoferrin display differential cell localization dynamics, but do not act as tumor markers or significantly affect the expression of other genes. Medicinal Chemistry. Vol. 2005;1(1): 57-64 (2005 ) .

Valiunas V, Bechberger JF, Naus CC, Brink PR, Goldberg GS Nontransformed cells can normalize gap junctional communication with transformed cells. Biochem Biophys Res Commun. Vol. 2005 Jul 22;333(1): 174-9 (2005 ) .

Alexander, D.B., Ichikawa, H., Bechberger, J.F., Valiunas, V., Ohki, M., Naus, C.C.G., Kunimoto, T., Tsuda, H., Miller, W.T., and Goldberg GS Normal cells control the growth of neighboring transformed cells independent of gap junctional communication and Src activity.. Cancer Res. Vol. 2004 Feb 15;64(4): 1347-58 (2004 ) .

Goldberg GS , Valiunas, V., and Brink, P.R Selective permeability of gap junction channels. Biochimica et Biophysica Acta. Vol. 2004 Mar 23;1662(1-2): 96-101 (2004 ) .

Alexander, D.B. and Goldberg GS Transfer of biologically important molecules between cells through gap junction channels.. Current Medicinal Chemistry . Vol. 2003 Oct;10(19): 2045-58 (2003 ) .

Goldberg GS , Alexander, D.B., Pellicena, P., Zhang, Z.-Y., Tsuda, H., and Miller, W.T. Src phosphorylates Cas on tyrosine 253 to promote migration of transformed cells. Journal of Biological Chemistry . Vol. 2003 Nov 21;278(47)Epub 2003 Sep 11: 46533-40 (2003 ) .

Goldberg GS , Moreno, A.P., and Lampe, P.D. Gap junctions between cells expressing connexin 43 or 32 show inverse permselectivity to adenosine and ATP. Journal of Biological Chemistry. Vol. 2002 Sep 27;277(39) Epub 2002 Jul 15.: 36725-30 (2002 ) .

Goldberg GS and Lampe, P.D. Capture of endogenous transjunctional metabolites. . In: Bruzzone R. and Giaume C. (Eds.) Methods in Molecular Biology: Connexin Channels Methods and Protocols,. Vol. Totowa NJ: Humana Press, Inc.: pp. 329-340 (2001 ) .

Goldberg GS , Jin, Z., Ichikawa, H., Naito, A., Ohki, M., El-Deiry, W., and Tsuda, H. Global effects of anchorage on gene expression during mammary carcinoma cell growth reveal role of tumor necrosis factor-related apoptosis inducing ligand in anoikis. Cancer Research . Vol. 2001 Feb 15;61(4): 1334-7 (2001 ) .

Goldberg GS , Bechberger, J.F., Tajima, Y., Omori, Y., Narayanan, R., Sanai, Y., Yamasaki, H., Naus, C.C.G., and Nicholson, B.J. Connexin43 suppresses MFG-E8 while inducing contact growth inhibition of glioma cells.. Cancer Research . Vol. 2000 Nov 1;60(21): 6018-26 (2000 ) .

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Grants and Contracts

Title: Src, Cas, Cx43 and gap junctional communication
Sponsor: UMDNJ Foundtion
Effective Date(s): 2007 - 2008
Role: P.I.

Title: Cell Communication and Growth Control (1 RO1 CA88805-01)
Sponsor: National Institutes of Health
Effective Date(s): 2002 - Ongoing
Role: P.I.

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Research Areas

Gap Junctional Communication: Connexins are integral membrane proteins which have evolved into a family of over 20 mammalian members that are most commonly referred to by their molecular weights. These proteins combine with each other to produce channels that directly connect the cytoplasm of adjacent cells. These channels, called gap junctions, enable cells to communicate with each other by sharing hydrophilic molecules of up to around 1 kD in size. Gap junctional communication is necessary for healthy development and homeostasis. Abnormal connexin phenotypes can result in several diseases. Therefore, it is important to understand how cells communicate with each other by gap junctions. We are studying how gap junctional communication is controlled, and the signals that pass between cells through gap junctions. Our experimental systems are geared to investigate lens development, cataracts, and cancer. However, this research is pertinent to many other processes including anatomical morphogenesis, heart development, neuronal disorders, skin disease, and deafness.

Other Intercellular Junctions: It has become clear that different types of intercellular junctions interact with each other to control many facets of cell growth and behavior. We are investigating mechanisms by which cadherins interact with integrins and other cellular structures to affect cell growth and migration. This work is designed to elucidate novel reagents and protocols to combat several kinds of cancer

Integrin Signaling: In general, nontransformed cells are anchorage independent, and can only survive and proliferate in the appropriate microenvironment. In contrast, most cancer cells overcome this dependency to become capable of nonanchored growth and migration. These hallmarks of transformed cell growth underlie the ability of cancer cells to become malignant and metastatic. We are currently elucidating mechanisms by which integrins interact with other proteins, including signal transduction kinases and cytoskeletal components, to control these events. These studies are designed to understand fundamental processes that differentiate cancer cells from their nontransformed precursors.

Receptor Signaling: In addition to intercellular junctions, cell growth and behavior can be controlled by diffusible factors. We are currently identifying novel factors that control tumor cell growth. This work should lead to innovative ways to detect and treat many kinds of cancer.

Signal Transduction: Ultimately, extracellular signals transmitted by junctional contact or diffusible factors must be transduced inside the cell to exert measurable effects. We are performing global, comprehensive, and nonbiased analyses to understand how this occurs. These studies are identifying novel tumor suppressor genes, as well as genes that promote nonanchored cell growth and migration. Results from this work is leading to the development of new biomarkers to detect specific types of caner, as well as reagents that may be used to suppress cancer progression.

Contact Normalization: Intercellular junctions mediate signals that allow normal cells to inhibit the transformed growth of neighboring tumor cells. The process is called Contact Normalization. Intimate junctional contact between tumor cells and normal cells is needed for this form of growth control. We are defining the role of cell junctions, including connexins, integrins, and cadherins, in this phenomenon. The long term goals of this work are to identify tumor markers and chemotherapeutic targets, and to develop agents that specifically block cancer cell growth without harming other cells in the body.

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