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Full-Text Articles in Medicine and Health Sciences
Loss Of Tumor Suppressor Tmem127 Drives Ret-Mediated Transformation Through Disrupted Membrane Dynamics, Timothy J Walker, Eduardo Reyes-Alvarez, Brandy D Hyndman, Michael G Sugiyama, Larissa C B Oliveira, Aisha N Rekab, Mathieu J F Crupi, Rebecca Cabral-Dias, Qianjin Guo, Patricia L M Dahia, Douglas S Richardson, Costin N Antonescu, Lois M Mulligan
Loss Of Tumor Suppressor Tmem127 Drives Ret-Mediated Transformation Through Disrupted Membrane Dynamics, Timothy J Walker, Eduardo Reyes-Alvarez, Brandy D Hyndman, Michael G Sugiyama, Larissa C B Oliveira, Aisha N Rekab, Mathieu J F Crupi, Rebecca Cabral-Dias, Qianjin Guo, Patricia L M Dahia, Douglas S Richardson, Costin N Antonescu, Lois M Mulligan
Journal Articles
Internalization from the cell membrane and endosomal trafficking of receptor tyrosine kinases (RTKs) are important regulators of signaling in normal cells that can frequently be disrupted in cancer. The adrenal tumor pheochromocytoma (PCC) can be caused by activating mutations of the rearranged during transfection (RET) receptor tyrosine kinase, or inactivation of TMEM127, a transmembrane tumor suppressor implicated in trafficking of endosomal cargos. However, the role of aberrant receptor trafficking in PCC is not well understood. Here, we show that loss of TMEM127 causes wildtype RET protein accumulation on the cell surface, where increased receptor density facilitates constitutive ligand-independent activity and …
Zinc Treatment Reverses And Anti-Zn-Regulated Mirs Suppress Esophageal Carcinomas In Vivo, Louise Fong, Kay Huebner, Ruiyan Jing, Karl Smalley, Christopher R Brydges, Oliver Fiehn, John Farber, Carlo M Croce
Zinc Treatment Reverses And Anti-Zn-Regulated Mirs Suppress Esophageal Carcinomas In Vivo, Louise Fong, Kay Huebner, Ruiyan Jing, Karl Smalley, Christopher R Brydges, Oliver Fiehn, John Farber, Carlo M Croce
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% …
Differentiation Of Fetal Hematopoietic Stem Cells Requires Arid4b To Restrict Autocrine Kitlg/Kit-Src Signaling., In-Chi Young, Bogang Wu, Jaclyn Andricovich, Sung-Ting Chuang, Rong Li, Alexandros Tzatsos, Ray-Chang Wu, Mei-Yi Wu
Differentiation Of Fetal Hematopoietic Stem Cells Requires Arid4b To Restrict Autocrine Kitlg/Kit-Src Signaling., In-Chi Young, Bogang Wu, Jaclyn Andricovich, Sung-Ting Chuang, Rong Li, Alexandros Tzatsos, Ray-Chang Wu, Mei-Yi Wu
Anatomy and Regenerative Biology Faculty Publications
No abstract provided.
Glutathione De Novo Synthesis But Not Recycling Process Coordinates With Glutamine Catabolism To Control Redox Homeostasis And Directs Murine T Cell Differentiation, Gaojian Lian, J. N. Rashida Gnanaprakasam, Tingting Wang, Ruohan Wu, Xuyong Chen, Lingling Liu, Yuqing Shen, Mao Yang, Jun Yang, Ying Chen, Vasilis Vasiliou, Teresa A. Cassel, Douglas R. Green, Yusen Liu, Teresa W. -M. Fan, Ruoning Wang
Glutathione De Novo Synthesis But Not Recycling Process Coordinates With Glutamine Catabolism To Control Redox Homeostasis And Directs Murine T Cell Differentiation, Gaojian Lian, J. N. Rashida Gnanaprakasam, Tingting Wang, Ruohan Wu, Xuyong Chen, Lingling Liu, Yuqing Shen, Mao Yang, Jun Yang, Ying Chen, Vasilis Vasiliou, Teresa A. Cassel, Douglas R. Green, Yusen Liu, Teresa W. -M. Fan, Ruoning Wang
Toxicology and Cancer Biology Faculty Publications
Upon antigen stimulation, T lymphocytes undergo dramatic changes in metabolism to fulfill the bioenergetic, biosynthetic and redox demands of proliferation and differentiation. Glutathione (GSH) plays an essential role in controlling redox balance and cell fate. While GSH can be recycled from Glutathione disulfide (GSSG), the inhibition of this recycling pathway does not impact GSH content and murine T cell fate. By contrast, the inhibition of the de novo synthesis of GSH, by deleting either the catalytic (Gclc) or the modifier (Gclm) subunit of glutamate–cysteine ligase (Gcl), dampens intracellular GSH, increases ROS, and impact T cell differentiation. Moreover, the inhibition of …
Abl Kinase Regulation By Braf/Erk And Cooperation With Akt In Melanoma, Aditi Jain, Rakshamani Tripathi, Courtney P. Turpin, Chi Wang, Rina Plattner
Abl Kinase Regulation By Braf/Erk And Cooperation With Akt In Melanoma, Aditi Jain, Rakshamani Tripathi, Courtney P. Turpin, Chi Wang, Rina Plattner
Pharmacology and Nutritional Sciences Faculty Publications
The melanoma incidence continues to increase, and the disease remains incurable for many due to its metastatic nature and high rate of therapeutic resistance. In particular, melanomas harboring BRAFV600E and PTEN mutations often are resistant to current therapies, including BRAF inhibitors (BRAFi) and immune checkpoint inhibitors. Abl kinases (Abl/Arg) are activated in melanomas and drive progression; however, their mechanism of activation has not been established. Here we elucidate a novel link between BRAFV600E/ERK signaling and Abl kinases. We demonstrate that BRAFV600E/ERK play a critical role in binding, phosphorylating and regulating Abl localization and Abl/Arg activation …
Relb Expression Determines The Differential Effects Of Ascorbic Acid In Normal And Cancer Cells, Xiaowei Wei, Yong Xu, Fang Fang Xu, Luksana Chaiswing, David M. Schnell, Teresa Noel, Chi Wang, Jinfei Chen, Daret K. St. Clair, William H. St. Clair
Relb Expression Determines The Differential Effects Of Ascorbic Acid In Normal And Cancer Cells, Xiaowei Wei, Yong Xu, Fang Fang Xu, Luksana Chaiswing, David M. Schnell, Teresa Noel, Chi Wang, Jinfei Chen, Daret K. St. Clair, William H. St. Clair
Toxicology and Cancer Biology Faculty Publications
Cancer cells typically experience higher oxidative stress than normal cells, such that elevating pro-oxidant levels can trigger cancer cell death. Although pre-exposure to mild oxidative agents will sensitize cancer cells to radiation, this pre-exposure may also activate the adaptive stress defense system in normal cells. Ascorbic acid is a prototype redox modulator that when infused intravenously appears to kill cancers without injury to normal tissues; however, the mechanisms involved remain elusive. In this study, we show how ascorbic acid kills cancer cells and sensitizes prostate cancer to radiation therapy while also conferring protection upon normal prostate epithelial cells against radiation-induced …
Crispr-Cas9 Mediated Nox4 Knockout Inhibits Cell Proliferation And Invasion In Hela Cells, Naser Jafari, Hyunju Kim, Rackhyun Park, Liqing Li, Minsu Jang, Andrew J. Morris, Junsoo Park, Cai Huang
Crispr-Cas9 Mediated Nox4 Knockout Inhibits Cell Proliferation And Invasion In Hela Cells, Naser Jafari, Hyunju Kim, Rackhyun Park, Liqing Li, Minsu Jang, Andrew J. Morris, Junsoo Park, Cai Huang
Markey Cancer Center Faculty Publications
Increased expression of NOX4 protein is associated with cancer progression and metastasis but the role of NOX4 in cell proliferation and invasion is not fully understood. We generated NOX4 knockout HeLa cell lines using the CRISPR-Cas9 gene editing system to explore the cellular functions of NOX4. After transfection of CRISPR-Cas9 construct, we performed T7 endonuclease 1 assays and DNA sequencing to generate and identify insertion and deletion of the NOX4 locus. We confirmed the knockout of NOX4 by Western blotting. NOX4 knockout cell lines showed reduced cell proliferation with an increase of sub-G1 cell population and the decrease of S/G2/M …
Evidence That A Lipolytic Enzyme—Hematopoietic-Specific Phospholipase C-Β2—Promotes Mobilization Of Hematopoietic Stem Cells By Decreasing Their Lipid Raft-Mediated Bone Marrow Retention And Increasing The Promobilizing Effects Of Granulocytes, M. Adamiak, A. Poniewierska-Baran, S. Borkowska, G. Schneider, A. Abdelbaset-Ismail, M. Suszynska, Ahmed Abdel-Latif, M. Kucia, J. Ratajczak, M. Z. Ratajczak
Evidence That A Lipolytic Enzyme—Hematopoietic-Specific Phospholipase C-Β2—Promotes Mobilization Of Hematopoietic Stem Cells By Decreasing Their Lipid Raft-Mediated Bone Marrow Retention And Increasing The Promobilizing Effects Of Granulocytes, M. Adamiak, A. Poniewierska-Baran, S. Borkowska, G. Schneider, A. Abdelbaset-Ismail, M. Suszynska, Ahmed Abdel-Latif, M. Kucia, J. Ratajczak, M. Z. Ratajczak
Internal Medicine Faculty Publications
Hematopoietic stem/progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment and are retained there by the interaction of membrane lipid raft-associated receptors, such as the α-chemokine receptor CXCR4 and the α4β1-integrin (VLA-4, very late antigen 4 receptor) receptor, with their respective specific ligands, stromal-derived factor 1 and vascular cell adhesion molecule 1, expressed in BM stem cell niches. The integrity of the lipid rafts containing these receptors is maintained by the glycolipid glycosylphosphatidylinositol anchor (GPI-A). It has been reported that a cleavage fragment of the fifth component of the activated complement cascade, C5a, has an …