Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 31

Publication Record

Connections

Is a Tumor Suppressor Gene in Colorectal Cancer.
Chen MS, Lo YH, Chen X, Williams CS, Donnelly JM, Criss ZK, Patel S, Butkus JM, Dubrulle J, Finegold MJ, Shroyer NF
(2019) Mol Cancer Res 17: 697-708
MeSH Terms: Animals, Cell Line, Tumor, Colorectal Neoplasms, DNA-Binding Proteins, Genes, Tumor Suppressor, HCT116 Cells, HEK293 Cells, Heterografts, Humans, Male, Mice, Mice, Inbred NOD, Transcription Factors
Show Abstract · Added April 15, 2019
Colorectal cancer is the third most common cancer and the third leading cause of cancer death in the United States. Growth factor-independent 1 (GFI1) is a zinc finger transcriptional repressor responsible for controlling secretory cell differentiation in the small intestine and colon. GFI1 plays a significant role in the development of human malignancies, including leukemia, lung cancer, and prostate cancer. However, the role of GFI1 in colorectal cancer progression is largely unknown. Our results demonstrate that RNA and protein expression of GFI1 are reduced in advanced-stage nonmucinous colorectal cancer. Subcutaneous tumor xenograft models demonstrated that the reexpression of GFI1 in 4 different human colorectal cancer cell lines inhibits tumor growth. To further investigate the role of Gfi1 in colorectal tumorigenesis, we developed transgenic mice harboring a deletion of Gfi1 in the colon driven by CDX2-cre (Gfi1; CDX2-cre) and crossed them with Apc mice (Apc; Gfi1; CDX2-cre). Loss of Gfi1 significantly increased the total number of colorectal adenomas compared with littermate controls with an APC mutation alone. Furthermore, we found that compound (Apc; Gfi1; CDX2-cre) mice develop larger adenomas, invasive carcinoma, as well as hyperplastic lesions expressing the neuroendocrine marker chromogranin A, a feature that has not been previously described in APC-mutant tumors in mice. Collectively, these results demonstrate that acts as a tumor suppressor gene in colorectal cancer, where deficiency of Gfi1 promotes malignancy in the colon. IMPLICATIONS: These findings reveal that GFI1 functions as a tumor suppressor gene in colorectal tumorigenesis.
©2019 American Association for Cancer Research.
0 Communities
1 Members
0 Resources
13 MeSH Terms
Consider Changing the Horse for Your CAR-T?
Wilson MH
(2018) Mol Ther 26: 1873-1874
MeSH Terms: Animals, Antigens, CD19, Heterografts, Horses, Immunoglobulin G, Immunotherapy, Adoptive, T-Lymphocytes
Added December 13, 2018
0 Communities
1 Members
0 Resources
7 MeSH Terms
Ultrasound Measurement of Vascular Density to Evaluate Response to Anti-Angiogenic Therapy in Renal Cell Carcinoma.
Rojas JD, Papadopoulou V, Czernuszewicz TJ, Rajamahendiran RM, Chytil A, Chiang YC, Chong DC, Bautch VL, Rathmell WK, Aylward S, Gessner RC, Dayton PA
(2019) IEEE Trans Biomed Eng 66: 873-880
MeSH Terms: Angiogenesis Inhibitors, Angiography, Animals, Carcinoma, Renal Cell, Drug Monitoring, Female, Heterografts, Kidney, Kidney Neoplasms, Mice, Mice, Inbred NOD, Mice, SCID, Microvessels, Ultrasonography
Show Abstract · Added October 30, 2019
BACKGROUND - Functional and molecular changes often precede gross anatomical changes, so early assessment of a tumor's functional and molecular response to therapy can help reduce a patient's exposure to the side effects of ineffective chemotherapeutics or other treatment strategies.
OBJECTIVE - Our intent was to test the hypothesis that an ultrasound microvascular imaging approach might provide indications of response to therapy prior to assessment of tumor size.
METHODS - Mice bearing clear-cell renal cell carcinoma xenograft tumors were treated with antiangiogenic and Notch inhibition therapies. An ultrasound measurement of microvascular density was used to serially track the tumor response to therapy.
RESULTS - Data indicated that ultrasound-derived microvascular density can indicate response to therapy a week prior to changes in tumor volume and is strongly correlated with physiological characteristics of the tumors as measured by histology ([Formula: see text]). Furthermore, data demonstrated that ultrasound measurements of vascular density can determine response to therapy and classify between-treatment groups with high sensitivity and specificity.
CONCLUSION/SIGNIFICANCE - Results suggests that future applications utilizing ultrasound imaging to monitor tumor response to therapy may be able to provide earlier insight into tumor behavior from metrics of microvascular density rather than anatomical tumor size measurements.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling.
Fröse J, Chen MB, Hebron KE, Reinhardt F, Hajal C, Zijlstra A, Kamm RD, Weinberg RA
(2018) Cell Rep 24: 962-972
MeSH Terms: Animals, Breast Neoplasms, Cell Line, Tumor, Cytoskeletal Proteins, Epithelial-Mesenchymal Transition, Female, Heterografts, Humans, Lung Neoplasms, Male, Mice, Mice, Inbred NOD, Mice, SCID, Pancreatic Neoplasms, Sialoglycoproteins, Signal Transduction
Show Abstract · Added April 10, 2019
The epithelial-mesenchymal transition (EMT) endows carcinoma cells with traits needed to complete many of the steps leading to metastasis formation, but its contributions specifically to the late step of extravasation remain understudied. We find that breast cancer cells that have undergone an EMT extravasate more efficiently from blood vessels both in vitro and in vivo. Analysis of gene expression changes associated with the EMT program led to the identification of an EMT-induced cell-surface protein, podocalyxin (PODXL), as a key mediator of extravasation in mesenchymal breast and pancreatic carcinoma cells. PODXL promotes extravasation through direct interaction of its intracellular domain with the cytoskeletal linker protein ezrin. Ezrin proceeds to establish dorsal cortical polarity, enabling the transition of cancer cells from a non-polarized, rounded cell morphology to an invasive extravasation-competent shape. Hence, the EMT program can directly enhance the efficiency of extravasation and subsequent metastasis formation through a PODXL-ezrin signaling axis.
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Lactate Metabolism in Human Lung Tumors.
Faubert B, Li KY, Cai L, Hensley CT, Kim J, Zacharias LG, Yang C, Do QN, Doucette S, Burguete D, Li H, Huet G, Yuan Q, Wigal T, Butt Y, Ni M, Torrealba J, Oliver D, Lenkinski RE, Malloy CR, Wachsmann JW, Young JD, Kernstine K, DeBerardinis RJ
(2017) Cell 171: 358-371.e9
MeSH Terms: Animals, Blood Chemical Analysis, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Citric Acid Cycle, Disease Models, Animal, Female, Glyceric Acids, Heterografts, Humans, Lactic Acid, Lung Neoplasms, Male, Mice, Monocarboxylic Acid Transporters, Neoplasm Transplantation, Symporters
Show Abstract · Added March 28, 2019
Cancer cells consume glucose and secrete lactate in culture. It is unknown whether lactate contributes to energy metabolism in living tumors. We previously reported that human non-small-cell lung cancers (NSCLCs) oxidize glucose in the tricarboxylic acid (TCA) cycle. Here, we show that lactate is also a TCA cycle carbon source for NSCLC. In human NSCLC, evidence of lactate utilization was most apparent in tumors with high fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell-autonomous lactate uptake. Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates. The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo.
Copyright © 2017 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
Prevention of breast cancer skeletal metastases with parathyroid hormone.
Swami S, Johnson J, Bettinson LA, Kimura T, Zhu H, Albertelli MA, Johnson RW, Wu JY
(2017) JCI Insight 2:
MeSH Terms: Animals, Bone Neoplasms, Breast Neoplasms, Cell Line, Tumor, Cellular Microenvironment, Female, Gene Expression Profiling, Heterografts, Liver Neoplasms, Lung Neoplasms, Mice, Parathyroid Hormone, Splenic Neoplasms, Survival Analysis, X-Ray Microtomography
Show Abstract · Added March 26, 2019
Advanced breast cancer is frequently associated with skeletal metastases and accelerated bone loss. Recombinant parathyroid hormone [teriparatide, PTH(1-34)] is the first anabolic agent approved in the US for treatment of osteoporosis. While signaling through the PTH receptor in the osteoblast lineage regulates bone marrow hematopoietic niches, the effects of anabolic PTH on the skeletal metastatic niche are unknown. Here, we demonstrate, using orthotopic and intratibial models of 4T1 murine and MDA-MB-231 human breast cancer tumors, that anabolic PTH decreases both tumor engraftment and the incidence of spontaneous skeletal metastasis in mice. Microcomputed tomography and histomorphometric analyses revealed that PTH increases bone volume and reduces tumor engraftment and volume. Transwell migration assays with murine and human breast cancer cells revealed that PTH alters the gene expression profile of the metastatic niche, in particular VCAM-1, to inhibit recruitment of cancer cells. While PTH did not affect growth or migration of the primary tumor, it elicited several changes in the tumor gene expression profile resulting in a less metastatic phenotype. In conclusion, PTH treatment in mice alters the bone microenvironment, resulting in decreased cancer cell engraftment, reduced incidence of metastases, preservation of bone microarchitecture and prolonged survival.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Two distinct mTORC2-dependent pathways converge on Rac1 to drive breast cancer metastasis.
Morrison Joly M, Williams MM, Hicks DJ, Jones B, Sanchez V, Young CD, Sarbassov DD, Muller WJ, Brantley-Sieders D, Cook RS
(2017) Breast Cancer Res 19: 74
MeSH Terms: Animals, Breast Neoplasms, Cell Line, Tumor, Cell Movement, Disease Models, Animal, Female, Gene Amplification, Heterografts, Humans, Mechanistic Target of Rapamycin Complex 2, Mice, Mice, Transgenic, Neoplasm Metastasis, Neoplasm Staging, Prognosis, Proto-Oncogene Proteins c-akt, Rapamycin-Insensitive Companion of mTOR Protein, Receptor, ErbB-2, Signal Transduction, rac1 GTP-Binding Protein, rho Guanine Nucleotide Dissociation Inhibitor beta
Show Abstract · Added April 15, 2019
BACKGROUND - The importance of the mTOR complex 2 (mTORC2) signaling complex in tumor progression is becoming increasingly recognized. HER2-amplified breast cancers use Rictor/mTORC2 signaling to drive tumor formation, tumor cell survival and resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy. Cell motility, a key step in the metastatic process, can be activated by mTORC2 in luminal and triple negative breast cancer cell lines, but its role in promoting metastases from HER2-amplified breast cancers is not yet clear.
METHODS - Because Rictor is an obligate cofactor of mTORC2, we genetically engineered Rictor ablation or overexpression in mouse and human HER2-amplified breast cancer models for modulation of mTORC2 activity. Signaling through mTORC2-dependent pathways was also manipulated using pharmacological inhibitors of mTOR, Akt, and Rac. Signaling was assessed by western analysis and biochemical pull-down assays specific for Rac-GTP and for active Rac guanine nucleotide exchange factors (GEFs). Metastases were assessed from spontaneous tumors and from intravenously delivered tumor cells. Motility and invasion of cells was assessed using Matrigel-coated transwell assays.
RESULTS - We found that Rictor ablation potently impaired, while Rictor overexpression increased, metastasis in spontaneous and intravenously seeded models of HER2-overexpressing breast cancers. Additionally, migration and invasion of HER2-amplified human breast cancer cells was diminished in the absence of Rictor, or upon pharmacological mTOR kinase inhibition. Active Rac1 was required for Rictor-dependent invasion and motility, which rescued invasion/motility in Rictor depleted cells. Rictor/mTORC2-dependent dampening of the endogenous Rac1 inhibitor RhoGDI2, a factor that correlated directly with increased overall survival in HER2-amplified breast cancer patients, promoted Rac1 activity and tumor cell invasion/migration. The mTORC2 substrate Akt did not affect RhoGDI2 dampening, but partially increased Rac1 activity through the Rac-GEF Tiam1, thus partially rescuing cell invasion/motility. The mTORC2 effector protein kinase C (PKC)α did rescue Rictor-mediated RhoGDI2 downregulation, partially rescuing Rac-guanosine triphosphate (GTP) and migration/motility.
CONCLUSION - These findings suggest that mTORC2 uses two coordinated pathways to activate cell invasion/motility, both of which converge on Rac1. Akt signaling activates Rac1 through the Rac-GEF Tiam1, while PKC signaling dampens expression of the endogenous Rac1 inhibitor, RhoGDI2.
0 Communities
1 Members
0 Resources
MeSH Terms
In vivo evaluation of IGF1R/IR PET ligand [F]BMS-754807 in rodents.
Prabhakaran J, Dewey SL, McClure R, Simpson NR, Tantawy MN, Mann JJ, Pham W, Kumar JSD
(2017) Bioorg Med Chem Lett 27: 941-943
MeSH Terms: Animals, Fluorine Radioisotopes, Heterografts, Humans, Mice, Positron-Emission Tomography, Pyrazoles, Radioligand Assay, Rats, Receptor, IGF Type 1, Receptor, Insulin, Triazines
Show Abstract · Added March 21, 2018
In vivo evaluation of [F]BMS-754807 binding in mice and rats using microPET and biodistribution methods is described herein. The radioligand shows consistent binding characteristics, in vivo, in both species. Early time frames of the microPET images and time activity curves of brain indicate poor penetration of the tracer across the blood brain barrier (BBB) in both species. However, microPET experiments in mice and rats show high binding of the radioligand outside the brain to heart, pancreas and muscle, the organs known for higher expression of IGF1R/1R. Biodistribution analysis 2h after injection of [F]BMS-754807 in rats show negligible [F]defluorination as reflected by the low bone uptake and clearance from blood. Overall, the data indicate that [F]BMS-754807 can potentially be a radiotracer for the quantification of IGF1R/IR outside the brain using PET.
Copyright © 2017 Elsevier Ltd. All rights reserved.
0 Communities
2 Members
0 Resources
12 MeSH Terms
Hedgehog and TGFβ signaling converge on Gli2 to control bony invasion and bone destruction in oral squamous cell carcinoma.
Cannonier SA, Gonzales CB, Ely K, Guelcher SA, Sterling JA
(2016) Oncotarget 7: 76062-76075
MeSH Terms: Animals, Bone and Bones, Carcinoma, Squamous Cell, Cell Line, Tumor, Disease Models, Animal, Gene Expression, Hedgehog Proteins, Heterografts, Humans, Mice, Mouth Neoplasms, Neoplasm Invasiveness, Nuclear Proteins, Parathyroid Hormone-Related Protein, Signal Transduction, Transforming Growth Factor beta, Zinc Finger Protein Gli2
Show Abstract · Added April 26, 2017
Oral Squamous Cell Carcinoma (OSCC) is the sixth most common cancer worldwide. OSCC invasion into the lymph nodes and mandible correlates with increased rates of recurrence and lower overall survival. Tumors that infiltrate mandibular bone proliferate rapidly and induce bone destruction. While survival rates have increased 12% over the last 20 years, this improvement is attributed to general advances in prevention, earlier detection, and updated treatments. Additionally, despite decades of research, the molecular mechanisms of OSCC invasion into the mandible are not well understood. Parathyroid Hormone-related Protein (PTHrP), has been shown to be essential for mandibular invasion in OSCC animal models, and our previous studies demonstrate that the transcription factor Gli2 increases PTHrP expression in tumor metastasis to bone. In OSCC, we investigated regulators of Gli2, including Hedgehog, TGFβ, and Wnt signaling to elucidate how PTHrP expression is controlled. Here we show that canonical Hedgehog and TGFβ signaling cooperate to increase PTHrP expression and mandibular invasion in a Gli2-dependent manner. Additionally, in an orthotopic model of mandibular invasion, inhibition of Gli2 using shRNA resulted in a significant decrease of both PTHrP expression and bony invasion. Collectively, our findings demonstrate that multiple signaling pathways converge on Gli2 to mediate PTHrP expression and bony invasion, highlighting Gli2 as a therapeutic target to prevent bony invasion in OSCC.
0 Communities
2 Members
0 Resources
17 MeSH Terms
The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer.
Joseph JD, Darimont B, Zhou W, Arrazate A, Young A, Ingalla E, Walter K, Blake RA, Nonomiya J, Guan Z, Kategaya L, Govek SP, Lai AG, Kahraman M, Brigham D, Sensintaffar J, Lu N, Shao G, Qian J, Grillot K, Moon M, Prudente R, Bischoff E, Lee KJ, Bonnefous C, Douglas KL, Julien JD, Nagasawa JY, Aparicio A, Kaufman J, Haley B, Giltnane JM, Wertz IE, Lackner MR, Nannini MA, Sampath D, Schwarz L, Manning HC, Tantawy MN, Arteaga CL, Heyman RA, Rix PJ, Friedman L, Smith ND, Metcalfe C, Hager JH
(2016) Elife 5:
MeSH Terms: Animals, Antineoplastic Agents, Breast Neoplasms, Cell Line, Tumor, Cinnamates, Disease Models, Animal, Heterografts, Humans, Indazoles, Mice, Prospective Studies, Rats, Receptors, Estrogen, Treatment Outcome
Show Abstract · Added April 6, 2017
ER-targeted therapeutics provide valuable treatment options for patients with ER+ breast cancer, however, current relapse and mortality rates emphasize the need for improved therapeutic strategies. The recent discovery of prevalent ESR1 mutations in relapsed tumors underscores a sustained reliance of advanced tumors on ERα signaling, and provides a strong rationale for continued targeting of ERα. Here we describe GDC-0810, a novel, non-steroidal, orally bioavailable selective ER downregulator (SERD), which was identified by prospectively optimizing ERα degradation, antagonism and pharmacokinetic properties. GDC-0810 induces a distinct ERα conformation, relative to that induced by currently approved therapeutics, suggesting a unique mechanism of action. GDC-0810 has robust in vitro and in vivo activity against a variety of human breast cancer cell lines and patient derived xenografts, including a tamoxifen-resistant model and those that harbor ERα mutations. GDC-0810 is currently being evaluated in Phase II clinical studies in women with ER+ breast cancer.
0 Communities
2 Members
0 Resources
14 MeSH Terms