Medical Sciences Commons^™

Cancer Cell-Specific Cgas/Sting Signaling Pathway In The Era Of Advancing Cancer Cell Biology, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Pattern-recognition receptors (PRRs) are critical to recognizing endogenous and exogenous threats to mount a protective proinflammatory innate immune response. PRRs may be located on the outer cell membrane, cytosol, and nucleus. The cGAS/STING signaling pathway is a cytosolic PRR system. Notably, cGAS is also present in the nucleus. The cGAS-mediated recognition of cytosolic dsDNA and its cleavage into cGAMP activates STING. Furthermore, STING activation through its downstream signaling triggers different interferon-stimulating genes (ISGs), initiating the release of type 1 interferons (IFNs) and NF-κB-mediated release of proinflammatory cytokines and molecules. Activating cGAS/STING generates type 1 IFN, which may prevent cellular transformation …

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% …

Microrna-1 Attenuates The Growth And Metastasis Of Small Cell Lung Cancer Through Cxcr4/Foxm1/Rrm2 Axis, Parvez Khan, Jawed A. Siddiqui, Prakash Kshirsagar Dr., Ramakanth Chirravuri Venkata, Shailendra K. Maurya, Tamara Mirzapoiazova, Naveenkumar Perumal, Sanjib Chaudhary, Ranjana K. Kanchan, Mahek Fatima, Md Arafat Khan, Asad Ur Rehman, Imayavaramban Lakshmanan, Sidharth Mahapatra, Geoffrey A. Talmon, Prakash Kulkarni, Apar Kishor Ganti, Maneesh Jain, Ravi Salgia, Surinder K. Batra, Mohd W. Nasser

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive lung cancer subtype that is associated with high recurrence and poor prognosis. Due to lack of potential drug targets, SCLC patients have few therapeutic options. MicroRNAs (miRNAs) provide an interesting repertoire of therapeutic molecules; however, the identification of miRNAs regulating SCLC growth and metastasis and their precise regulatory mechanisms are not well understood.

METHODS: To identify novel miRNAs regulating SCLC, we performed miRNA-sequencing from donor/patient serum samples and analyzed the bulk RNA-sequencing data from the tumors of SCLC patients. Further, we developed a nanotechnology-based, highly sensitive method to detect microRNA-1 (miR-1, …

Androgen Receptor Inhibition Suppresses Anti-Tumor Neutrophil Response Against Bone Metastatic Prostate Cancer Via Regulation Of Tβri Expression, Massar Alsamraae, Diane Costanzo-Garvey, Benjamin A. Teply, Shawna Boyle, Gary Sommerville, Zachary T. Herbert, Colm Morrissey, Alicia J. Dafferner, Maher Y. Abdalla, Rachel W. Fallet, Tammy Kielian, Heather Jensen Smith, Edson I. Deoliveira, Keqiang Chen, Ian A. Bettencourt, Ji Ming Wang, Daniel W. Mcvicar, Tyler Keeley, Fang Yu, Leah M. Cook

Journal Articles: Pathology and Microbiology

Bone metastatic disease of prostate cancer (PCa) is incurable and progression in bone is largely dictated by tumor-stromal interactions in the bone microenvironment. We showed previously that bone neutrophils initially inhibit bone metastatic PCa growth yet metastatic PCa becomes resistant to neutrophil response. Further, neutrophils isolated from tumor-bone lost their ability to suppress tumor growth through unknown mechanisms. With this study, our goal was to define the impact of metastatic PCa on neutrophil function throughout tumor progression and to determine the potential of neutrophils as predictive biomarkers of metastatic disease. Using patient peripheral blood polymorphonuclear neutrophils (PMNs), we identified that …

Hypoxia Regulates Vessel-Modifying Macrophages And Vice Versa In Tumors, Kayla Jo Steinberger

Graduate Theses, Dissertations, and Problem Reports

Hypoxia, or low oxygen, is a common feature of solid tumors correlating with poor survival in cancer patients. Growing tumors need a blood supply to deliver oxygen. Tumors attempt to re-acquire oxygen by forming new blood vessels from nearby, pre-existing vessels, a process known as angiogenesis. Past treatments aimed at preventing this process yielded not only disappointing results in the clinic but sometimes worsened the patient’s prognosis making the tumor more hypoxic, emphasizing the urgent need for novel targets. In tumors, angiogenesis is notoriously dysfunctional resulting in leaky, under-perfused blood vessels which cannot adequately deliver oxygen and exacerbates hypoxia. Emerging …