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Full-Text Articles in Medicine and Health Sciences
Star-Related Lipid Transfer Protein 10 (Stard10): A Novel Key Player In Alcohol-Induced Breast Cancer Progression, Andrea Floris, Jia Luo, Jacqueline A. Frank, Jennifer Zhou, Sandro Orrù, Michela Biancolella, Sabina Pucci, Augusto Orlandi, Paolo Campagna, Antonella Balzano, Komal Ramani, Maria Lauda Tomasi
Star-Related Lipid Transfer Protein 10 (Stard10): A Novel Key Player In Alcohol-Induced Breast Cancer Progression, Andrea Floris, Jia Luo, Jacqueline A. Frank, Jennifer Zhou, Sandro Orrù, Michela Biancolella, Sabina Pucci, Augusto Orlandi, Paolo Campagna, Antonella Balzano, Komal Ramani, Maria Lauda Tomasi
Pharmacology and Nutritional Sciences Faculty Publications
Background: Ethanol abuse promotes breast cancer development, metastasis and recurrence stimulating mammary tumorigenesis by mechanisms that remain unclear. Normally, 35% of breast cancer is Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-positive that predisposes to poor prognosis and relapse, while ethanol drinking leads to invasion of their ERBB2 positive cells triggering the phosphorylation status of mitogen-activated protein kinase. StAR-related lipid transfer protein 10 (STARD10) is a lipid transporter of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); changes on membrane composition of PC and PE occur before the morphological tumorigenic events. Interestingly, STARD10 has been described to be highly expressed in 35–40% of ERBB2-positive breast …
Nanoparticle Orientation To Control Rna Loading And Ligand Display On Extracellular Vesicles For Cancer Regression, Fengmei Pi, Daniel W. Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr G. Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M. Croce, Bin Guo, B. Mark Evers, Peixuan Guo
Nanoparticle Orientation To Control Rna Loading And Ligand Display On Extracellular Vesicles For Cancer Regression, Fengmei Pi, Daniel W. Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr G. Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M. Croce, Bin Guo, B. Mark Evers, Peixuan Guo
Markey Cancer Center Faculty Publications
Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for …
Nanoparticle Delivery Of Mir-34a Eradicates Long-Term-Cultured Breast Cancer Stem Cells Via Targeting C22orf28 Directly, Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P. Zhou, Mien-Chie Hung, Xiaoming Xie
Nanoparticle Delivery Of Mir-34a Eradicates Long-Term-Cultured Breast Cancer Stem Cells Via Targeting C22orf28 Directly, Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P. Zhou, Mien-Chie Hung, Xiaoming Xie
Molecular and Cellular Biochemistry Faculty Publications
Rationale: Cancer stem cells (CSCs) have been implicated as the seeds of therapeutic resistance and metastasis, due to their unique abilities of self-renew, wide differentiation potentials and resistance to most conventional therapies. It is a proactive strategy for cancer therapy to eradicate CSCs. Methods: Tumor tissue-derived breast CSCs (BCSC), including XM322 and XM607, were isolated by fluorescence-activated cell sorting (FACS); while cell line-derived BCSC, including MDA-MB-231.SC and MCF-7.SC, were purified by magnetic-activated cell sorting (MACS). Analyses of microRNA and mRNA expression array profiles were performed in multiple breast cell lines. The mentioned nanoparticles were constructed following the standard molecular cloning …
Loss Of Fructose-1,6-Bisphosphatase Induces Glycolysis And Promotes Apoptosis Resistance Of Cancer Stem-Like Cells: An Important Role In Hexavalent Chromium-Induced Carcinogenesis, Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo, Zhuo Zhang
Loss Of Fructose-1,6-Bisphosphatase Induces Glycolysis And Promotes Apoptosis Resistance Of Cancer Stem-Like Cells: An Important Role In Hexavalent Chromium-Induced Carcinogenesis, Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo, Zhuo Zhang
Toxicology and Cancer Biology Faculty Publications
Hexavalent chromium (Cr(VI)) compounds are confirmed human carcinogens for lung cancer. Our previous studies has demonstrated that chronic exposure of human bronchial epithelial BEAS-2B cells to low dose of Cr(VI) causes malignant cell transformation. The acquisition of cancer stem cell-like properties is involved in the initiation of cancers. The present study has observed that a small population of cancer stem-like cells (BEAS-2B-Cr-CSC) exists in the Cr(VI)-transformed cells (BEAS-2B-Cr). Those BEAS-2B-Cr-CSC exhibit extremely reduced capability of generating reactive oxygen species (ROS) and apoptosis resistance. BEAS-2B-Cr-CSC are metabolic inactive as evidenced by reductions in oxygen consumption, glucose uptake, ATP production, and lactate …
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 …
A Naturally Generated Decoy Of The Prostate Apoptosis Response-4 Protein Overcomes Therapy Resistance In Tumors, Nikhil Hebbar, Ravshan Burikhanov, Nidhi Shukla, Shirley Qiu, Yanming Zhao, Kojo S. J. Elenitoba-Johnson, Vivek M. Rangnekar
A Naturally Generated Decoy Of The Prostate Apoptosis Response-4 Protein Overcomes Therapy Resistance In Tumors, Nikhil Hebbar, Ravshan Burikhanov, Nidhi Shukla, Shirley Qiu, Yanming Zhao, Kojo S. J. Elenitoba-Johnson, Vivek M. Rangnekar
Radiation Medicine Faculty Publications
Primary tumors are often heterogeneous, composed of therapy-sensitive and emerging therapy-resistant cancer cells. Interestingly, treatment of therapy-sensitive tumors in heterogeneous tumor microenvironments results in apoptosis of therapy-resistant tumors. In this study, we identify a prostate apoptosis response-4 (Par-4) amino-terminal fragment (PAF) that is released by diverse therapy-sensitive cancer cells following therapy-induced caspase cleavage of the tumor suppressor Par-4 protein. PAF caused apoptosis in cancer cells resistant to therapy and inhibited tumor growth. A VASA segment of Par-4 mediated its binding and degradation by the ubiquitin ligase Fbxo45, resulting in loss of Par-4 proapoptotic function. Conversely, PAF, which contains this VASA …
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 …
Cellular And Molecular Mechanisms Underlying Alcohol-Induced Aggressiveness Of Breast Cancer, Yongchao Wang, Mei Xu, Zun-Ji Ke, Jia Luo
Cellular And Molecular Mechanisms Underlying Alcohol-Induced Aggressiveness Of Breast Cancer, Yongchao Wang, Mei Xu, Zun-Ji Ke, Jia Luo
Pharmacology and Nutritional Sciences Faculty Publications
Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the progression and aggressiveness of existing mammary tumors. Recent progress in this line of research suggests that alcohol exposure is associated with invasive breast cancer and promotes the growth and metastasis of mammary tumors. There are multiple potential mechanisms involved in alcohol-stimulated progression and aggressiveness of breast cancer. Alcohol may increase the mobility …
Pleckstrin Homology (Ph) Domain Leucine-Rich Repeat Protein Phosphatase Controls Cell Polarity By Negatively Regulating The Activity Of Atypical Protein Kinase C, Xiaopeng Xiong, Xin Li, Yang-An Wen, Tianyan Gao
Pleckstrin Homology (Ph) Domain Leucine-Rich Repeat Protein Phosphatase Controls Cell Polarity By Negatively Regulating The Activity Of Atypical Protein Kinase C, Xiaopeng Xiong, Xin Li, Yang-An Wen, Tianyan Gao
Markey Cancer Center Faculty Publications
The proper establishment of epithelial polarity allows cells to sense and respond to signals that arise from the microenvironment in a spatiotemporally controlled manner. Atypical PKCs (aPKCs) are implicated as key regulators of epithelial polarity. However, the molecular mechanism underlying the negative regulation of aPKCs remains largely unknown. In this study, we demonstrated that PH domain leucine-rich repeat protein phosphatase (PHLPP), a novel family of Ser/Thr protein phosphatases, plays an important role in regulating epithelial polarity by controlling the phosphorylation of both aPKC isoforms. Altered expression of PHLPP1 or PHLPP2 disrupted polarization of Caco2 cells grown in 3D cell cultures …
P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A Brekken, Craig W. Vander Kooi, Arthur M. Mercurio
P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A Brekken, Craig W. Vander Kooi, Arthur M. Mercurio
Molecular and Cellular Biochemistry Faculty Publications
Autocrine VEGF signaling is critical for sustaining prostate and other cancer stem cells (CSCs), and it is a potential therapeutic target, but we observed that CSCs isolated from prostate tumors are resistant to anti-VEGF (bevacizumab) and anti-VEGFR (sunitinib) therapy. Intriguingly, resistance is mediated by VEGF/neuropilin signaling, which is not inhibited by bevacizumab and sunitinib, and it involves the induction of P-Rex1, a Rac GEF, and consequent Rac1-mediated ERK activation. This induction of P-Rex1 is dependent on Myc. CSCs isolated from the PTENpc−/− transgenic model of prostate cancer exhibit Rac1-dependent resistance to bevacizumab. Rac1 inhibition or P-Rex1 downregulation increases the …
Targeting Wnt/Β-Catenin Pathway In Hepatocellular Carcinoma Treatment, Valery Vilchez, Lilia M. Turcios, Francesc Marti, Roberto Gedaly
Targeting Wnt/Β-Catenin Pathway In Hepatocellular Carcinoma Treatment, Valery Vilchez, Lilia M. Turcios, Francesc Marti, Roberto Gedaly
Surgery Faculty Publications
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/β-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug …
Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers
Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers
Markey Cancer Center Faculty Publications
Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of …
A Shared Gene Expression Signature In Mouse Models Of Ebv-Associated And Non-Ebv-Associated Burkitt Lymphoma, Kathryn T. Bieging, Kamonwan Fish, Subbarao Bondada, Richard Longnecker
A Shared Gene Expression Signature In Mouse Models Of Ebv-Associated And Non-Ebv-Associated Burkitt Lymphoma, Kathryn T. Bieging, Kamonwan Fish, Subbarao Bondada, Richard Longnecker
Microbiology, Immunology, and Molecular Genetics Faculty Publications
The link between EBV infection and Burkitt lymphoma (BL) is strong, but the mechanism underlying that link has been elusive. We have developed a mouse model for EBV-associated BL in which LMP2A, an EBV latency protein, and MYC are expressed in B cells. Our model has demonstrated the ability of LMP2A to accelerate tumor onset, increase spleen size, and bypass p53 inactivation. Here we describe the results of total gene expression analysis of tumor and pretumor B cells from our transgenic mouse model. Although we see many phenotypic differences and changes in gene expression in pretumor B cells, the transcriptional …