Protein Kinase C Signaling Mechanisms in Cancer

Summary

Principal Investigator: Alan P Fields
Abstract: DESCRIPTION (provided by applicant): Our long-term goals are to elucidate protein kinase C (PKC) signaling mechanisms that contribute to cancer and translate these mechanistic insights into better prognostic and treatment strategies. In previous funding periods, we discovered that PKC? is an oncogene in non-small cell lung cancer (NSCLC) the leading cause of cancer death in the United States, elucidated a major oncogenic PKC? signaling pathway, and developed a therapeutic agent that targets oncogenic PKC? signaling that is currently being evaluated in the clinic. During the current funding period we showed that: 1) PKC? forms an oncogenic PKC?/Par6 signaling complex in the cytoplasm of NSCLC cells that is necessary for cell proliferation and invasion in vitro, and tumor formation in vivo;2) the guanine nucleotide exchange factor (GEF) Ect2 binds the PKC?/Par6 complex and activates Rac1, a key downstream effector of this complex;3) PKC? regulates the intracellular location and oncogenic activity of Ect2 through direct binding and phosphorylation;4) matrix metalloproteinase 10 (Mmp10) is a critical downstream effector of the PKC?/Ect2/Par6/Rac1 signaling axis that is required for NSCLC cell proliferation and invasion in vitro, and Kras-mediated lung tumorigenesis in vivo;and 5) both PKC? and Mmp10 are required for Kras-mediated transformation of bronchio-alveolar stem cells (BASCs), putative lung tumorinitiating cells (TICs) in vivo. Our preliminary studies indicate that: 1) the PKC?/Ect2/Par6/Rac1/Mmp10 signaling axis maintains a tumor-initiating cell phenotype in NSCLC cells characterized by stem-like behavior and enhanced tumorigenicity;2) a significant pool of cellular Ect2 localizes to the nucleolus in a PKC?- dependent manner where it regulates ribosomal RNA (rRNA) transcription;3) PKC? transcriptionally activates cell autonomous hedgehog (Hh) signaling in NSCLC tumor-initiating cells;and 4) PKC? regulates recruitment of the stem cell pluripotency factor Sox2 to th promoter region of the gene encoding Hedgehog Acyl Transferase (HHAT), an enzyme that catalyzes a key step in the production of Hh ligand. Based on these data, we hypothesize that: 1) PKC?-mediated transformation involves regulation of Ect2 nucleolar localization and pre-ribosomal RNA synthesis;2) Ect2 signaling is required for Kras-mediated BASC transformation and lung tumorigenesis in vivo;3) PKC? maintains a lung tumor-initiating cell phenotype, at least in part, through Sox2-mediated induction of HHAT transcription and activation of a cell autonomous Hh signaling axis;and 4) HHAT, a PKC?-dependent transcriptional target, plays a key role in lung tumor-initiating activity in vivo. These hypotheses will be tested through completion of four interrelated specific aims to: 1) determine the mechanism by which PKC? and Ect2 regulate ribosomal RNA transcription;2) assess the role of Ect2 in Kras-mediated lung tumorigenesis;3) determine the mechanism by which PKC? regulates hedgehog acyl-transferase (HHAT) expression;and 4) assess the role of HHAT in lung tumorigenesis.
Funding Period: 1999-04-02 - 2018-04-30
more information: NIH RePORT

Top Publications

  1. ncbi Differential expression, distribution, and function of PPAR-gamma in the proximal and distal colon
    Weidong Su
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida 32225, USA
    Physiol Genomics 30:342-53. 2007
  2. pmc Protein kinase C iota in the intestinal epithelium protects against dextran sodium sulfate-induced colitis
    Shelly R Calcagno
    Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, USA
    Inflamm Bowel Dis 17:1685-97. 2011
  3. pmc Matrix metalloproteinase-10 promotes Kras-mediated bronchio-alveolar stem cell expansion and lung cancer formation
    Roderick P Regala
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida, United States of America
    PLoS ONE 6:e26439. 2011
  4. pmc Protein kinase Cα promotes cell migration through a PDZ-dependent interaction with its novel substrate discs large homolog 1 (DLG1)
    Audrey K O'Neill
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 286:43559-68. 2011
  5. pmc Correction of metabolic abnormalities in a rodent model of obesity, metabolic syndrome, and type 2 diabetes mellitus by inhibitors of hepatic protein kinase C-ι
    Mini P Sajan
    Medical and Research Services, James A Haley Veterans Medical Center, Tampa, FL 33612, USA
    Metabolism 61:459-69. 2012
  6. pmc Protein kinase C iota as a therapeutic target in alveolar rhabdomyosarcoma
    K Kikuchi
    Pediatric Cancer Biology Program, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239 3098, USA
    Oncogene 32:286-95. 2013
  7. pmc Protein kinase C iota regulates pancreatic acinar-to-ductal metaplasia
    Michele L Scotti
    Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America
    PLoS ONE 7:e30509. 2012
  8. pmc Matrix metalloproteinase-10 (MMP-10) interaction with tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2: binding studies and crystal structure
    Jyotica Batra
    Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida 32224, USA
    J Biol Chem 287:15935-46. 2012
  9. pmc Matrix metalloproteinase-10 is required for lung cancer stem cell maintenance, tumor initiation and metastatic potential
    Verline Justilien
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida, United States of America
    PLoS ONE 7:e35040. 2012
  10. pmc Matrix metalloproteinase induction of Rac1b, a key effector of lung cancer progression
    Melody L Stallings-Mann
    Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA
    Sci Transl Med 4:142ra95. 2012

Research Grants

  1. Regulation of Tumorigenesis and therapeutic resistance by Nrf2 in lung cancer
    Shyam Biswal; Fiscal Year: 2013
  2. PROTON RADIATION THERAPY RESEARCH
    Thomas F DeLaney; Fiscal Year: 2013
  3. Wisconsin Center of Excellence in Genomics Science
    Michael Olivier; Fiscal Year: 2013
  4. CELLULAR AND MOLECULAR MECHANISMS OF GASTROINTESTINAL CANCERS
    Lopa Mishra; Fiscal Year: 2013
  5. Myofibroblasts in Gastrointestinal Cancers
    TIMOTHY CRAGIN WANG; Fiscal Year: 2013
  6. SPORE IN BREAST CANCER
    HENRY SHELTON EARP; Fiscal Year: 2013
  7. University of Maryland Greenebaum Cancer Center Support Grant
    Kevin J Cullen; Fiscal Year: 2013
  8. THERAPY OF LYMPHOMA/LEUKEMIA WITH MONOCLONAL ANTIBODIES
    Oliver W Press; Fiscal Year: 2013
  9. Optical Technologies and Molecular Imaging for Cervical Neoplasia
    Michele Follen; Fiscal Year: 2013
  10. HuR Targeted Nanotherapy for Lung Cancer
    Rajagopal Ramesh; Fiscal Year: 2013

Detail Information

Publications34

  1. ncbi Differential expression, distribution, and function of PPAR-gamma in the proximal and distal colon
    Weidong Su
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida 32225, USA
    Physiol Genomics 30:342-53. 2007
    ....
  2. pmc Protein kinase C iota in the intestinal epithelium protects against dextran sodium sulfate-induced colitis
    Shelly R Calcagno
    Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, USA
    Inflamm Bowel Dis 17:1685-97. 2011
    ..Therefore, intestinal epithelial barrier function is critically important, and disruption of the intestinal epithelium results in rapid repair of the damaged area...
  3. pmc Matrix metalloproteinase-10 promotes Kras-mediated bronchio-alveolar stem cell expansion and lung cancer formation
    Roderick P Regala
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida, United States of America
    PLoS ONE 6:e26439. 2011
    ..These results indicate that Mmp10 may represent a novel therapeutic approach to target lung cancer stem cells...
  4. pmc Protein kinase Cα promotes cell migration through a PDZ-dependent interaction with its novel substrate discs large homolog 1 (DLG1)
    Audrey K O'Neill
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 286:43559-68. 2011
    ..Taken together, these data establish the requirement of scaffolding to DLG1 for PKCα to promote cellular migration...
  5. pmc Correction of metabolic abnormalities in a rodent model of obesity, metabolic syndrome, and type 2 diabetes mellitus by inhibitors of hepatic protein kinase C-ι
    Mini P Sajan
    Medical and Research Services, James A Haley Veterans Medical Center, Tampa, FL 33612, USA
    Metabolism 61:459-69. 2012
    ....
  6. pmc Protein kinase C iota as a therapeutic target in alveolar rhabdomyosarcoma
    K Kikuchi
    Pediatric Cancer Biology Program, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239 3098, USA
    Oncogene 32:286-95. 2013
    ....
  7. pmc Protein kinase C iota regulates pancreatic acinar-to-ductal metaplasia
    Michele L Scotti
    Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America
    PLoS ONE 7:e30509. 2012
    ..Our results indicate that PKCι is an early marker of pancreatic neoplasia and suggest that PKCι is a potential downstream target of K-ras(G12D) in pancreatic ductal metaplasia in vivo...
  8. pmc Matrix metalloproteinase-10 (MMP-10) interaction with tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2: binding studies and crystal structure
    Jyotica Batra
    Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida 32224, USA
    J Biol Chem 287:15935-46. 2012
    ..This structural information may ultimately assist in the design of more selective TIMP-based inhibitors tailored for specificity toward individual members of the stromelysin family, with potential therapeutic applications...
  9. pmc Matrix metalloproteinase-10 is required for lung cancer stem cell maintenance, tumor initiation and metastatic potential
    Verline Justilien
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida, United States of America
    PLoS ONE 7:e35040. 2012
    ..Our data demonstrate for the first time that Mmp10 is a critical lung cancer stem cell gene and novel therapeutic target for lung cancer stem cells...
  10. pmc Matrix metalloproteinase induction of Rac1b, a key effector of lung cancer progression
    Melody L Stallings-Mann
    Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA
    Sci Transl Med 4:142ra95. 2012
    ..Rac1b is expressed abundantly in stages 1 and 2 of human lung adenocarcinomas and, hence, is an attractive molecular target for the development of new therapies that prevent progression to later-stage lung cancers...
  11. pmc Atypical protein kinase Cι is required for Wnt3a-dependent neurite outgrowth and binds to phosphorylated dishevelled 2
    Yoshimi Endo Greer
    From the Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Biol Chem 288:9438-46. 2013
    ..Taken together, these results suggest that site-specific Dvl2 phosphorylation is required for Dvl2 association with PKCι. This interaction is likely to be one of the mechanisms essential for Wnt3a-dependent neurite outgrowth...
  12. pmc Protein kinase Cα suppresses Kras-mediated lung tumor formation through activation of a p38 MAPK-TGFβ signaling axis
    K S Hill
    Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA
    Oncogene 33:2134-44. 2014
    ..Our results provide the first direct evidence that PKCα exhibits tumor suppressor activity in the lung in vivo. ..
  13. pmc Phase I dose escalation study of the PKCι inhibitor aurothiomalate for advanced non-small-cell lung cancer, ovarian cancer, and pancreatic cancer
    Aaron S Mansfield
    aDepartment of Medical Oncology, Mayo Clinic, Rochester, Minnesota bDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida cDepartment of Internal Medicine, Greater Baltimore Medical Center, Baltimore, Maryland dDepartment of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA
    Anticancer Drugs 24:1079-83. 2013
    ..In summary, this phase I study was successful in identifying ATM 50 mg intramuscularly weekly as the MTD. Future clinical investigations targeting PKCι are currently in progress...
  14. pmc Protein kinase C zeta regulates human pancreatic cancer cell transformed growth and invasion through a STAT3-dependent mechanism
    Amanda M Butler
    Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America
    PLoS ONE 8:e72061. 2013
    ....
  15. pmc PKCι maintains a tumor-initiating cell phenotype that is required for ovarian tumorigenesis
    Yin Wang
    Griffin Cancer Research Building, Rm 212, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224
    Mol Cancer Res 11:1624-35. 2013
    ..These data demonstrate that PKCι is required for a TIC phenotype in ovarian cancer, and that auranofin is an attractive therapeutic option to target deadly ovarian TICs in ovarian cancer patients...
  16. pmc Atypical protein kinase Cι as a human oncogene and therapeutic target
    Peter J Parker
    London Research Institute, Lincoln s Inn Fields, London WC2A 3LY, UK King s College London, Guy s Campus, London, UK
    Biochem Pharmacol 88:1-11. 2014
    ..In this review, we discuss the role of PKCiota in transformation and describe mechanism-based approaches to therapeutically target oncogenic PKCiota signaling in cancer. ..
  17. pmc Oncogenic activity of Ect2 is regulated through protein kinase C iota-mediated phosphorylation
    Verline Justilien
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    J Biol Chem 286:8149-57. 2011
    ..Our data support a model in which PKCι-mediated phosphorylation regulates Ect2 binding to the oncogenic PKCι-Par6 complex thereby activating Rac1 activity and driving transformed growth and invasion...
  18. pmc Protein kinase Cι expression and oncogenic signaling mechanisms in cancer
    Nicole R Murray
    Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida 32224, USA
    J Cell Physiol 226:879-87. 2011
    ....
  19. pmc Protein kinase C iota: human oncogene, prognostic marker and therapeutic target
    Alan P Fields
    Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA
    Pharmacol Res 55:487-97. 2007
    ..Throughout, we identify key unanswered questions and exciting future avenues of investigation regarding this important oncogenic molecule...
  20. pmc Rit mutants confirm role of MEK/ERK signaling in neuronal differentiation and reveal novel Par6 interaction
    Jennifer L Rudolph
    Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, 741 South Limestone Street, Lexington, KY 40536 0509, USA
    Biochim Biophys Acta 1773:1793-800. 2007
    ..In addition, in vivo binding studies identified a novel mechanism of Par6 interaction, suggesting that the cell polarity machinery may serve to spatially restrict Rit signaling...
  21. pmc Oncogenic K-ras promotes early carcinogenesis in the mouse proximal colon
    Shelly R Calcagno
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    Int J Cancer 122:2462-70. 2008
    ..Our data indicate that acquisition of a K-ras mutation is an initiating neoplastic event in proximal colon cancer development in mice...
  22. pmc Matrix metalloproteinase-10 is a critical effector of protein kinase Ciota-Par6alpha-mediated lung cancer
    L A Frederick
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    Oncogene 27:4841-53. 2008
    ..Our data define a PKCiota-Par6alpha-Rac1 signaling axis that drives anchorage-independent growth and invasion of NSCLC cells through induction of MMP-10 expression...
  23. pmc The high affinity peroxisome proliferator-activated receptor-gamma agonist RS5444 inhibits both initiation and progression of colon tumors in azoxymethane-treated mice
    Weidong Su
    Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA
    Int J Cancer 123:991-7. 2008
    ..We conclude that RS5444 inhibits both initiation and progression of colon tumors in the AOM model of sporadic colon carcinogenesis...
  24. pmc Atypical protein kinase C iota expression and aurothiomalate sensitivity in human lung cancer cells
    Roderick P Regala
    Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida 32224, USA
    Cancer Res 68:5888-95. 2008
    ..Our results indicate that PKC iota expression profiling will be useful in identifying lung cancer patients most likely to respond to ATM therapy in an ongoing clinical trial...
  25. pmc Protein kinase C betaII and PKCiota/lambda: collaborating partners in colon cancer promotion and progression
    Nicole R Murray
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    Cancer Res 69:656-62. 2009
    ..Thus, PKCbetaII and PKCiota, whose expression is elevated in both rodent and human colon tumors, collaborate to drive colon tumor formation and progression, respectively...
  26. pmc Protein kinase Cbeta is an effective target for chemoprevention of colon cancer
    Alan P Fields
    Departments of Cancer Biology and Pathology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    Cancer Res 69:1643-50. 2009
    ..Thus, PKCbetaII is an important target for colon cancer chemoprevention and the PKCbeta-selective inhibitor enzastaurin may represent an effective chemopreventive agent in patients at high risk for colon cancer...
  27. pmc Meta-analysis of oncogenic protein kinase Ciota signaling in lung adenocarcinoma
    Eda Erdogan
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    Clin Cancer Res 15:1527-33. 2009
    ..Atypical protein kinase Ciota (PKCiota) is an oncogene in non-small cell lung cancer (NSCLC). Here, we identify four functional gene targets of PKCiota in lung adenocarcinoma (LAC), the most prominent form of NSCLC...
  28. pmc Ect2 links the PKCiota-Par6alpha complex to Rac1 activation and cellular transformation
    V Justilien
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    Oncogene 28:3597-607. 2009
    ..Our data indicate that Ect2 and PKCiota are genetically and functionally linked in NSCLC, acting to coordinately drive tumor cell proliferation and invasion through formation of an oncogenic PKCiota-Par6alpha-Ect2 complex...
  29. pmc Atypical protein kinase C{iota} is required for bronchioalveolar stem cell expansion and lung tumorigenesis
    Roderick P Regala
    Departments of Cancer Biology and Pathology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida, USA
    Cancer Res 69:7603-11. 2009
    ..These data have important implications for PKCiota as a therapeutic target and for the clinical use of aurothiomalate for lung cancer treatment...
  30. pmc Protein kinase Ciota is required for pancreatic cancer cell transformed growth and tumorigenesis
    Michele L Scotti
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    Cancer Res 70:2064-74. 2010
    ..Our results strongly indicate that PKCiota will be an effective target for pancreatic cancer therapy...
  31. pmc Splice variants of SmgGDS control small GTPase prenylation and membrane localization
    Tracy J Berg
    Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    J Biol Chem 285:35255-66. 2010
    ..These results indicate that guanine nucleotide exchange and interactions with SmgGDS splice variants can regulate the entrance and passage of PBR-possessing small GTPases through the prenylation pathway...
  32. pmc The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate Hedgehog signaling in lung squamous cell carcinoma
    Verline Justilien
    Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA
    Cancer Cell 25:139-51. 2014
    ..Thus, PKCι and SOX2 are genetically, biochemically, and functionally linked in LSCC, and together they drive tumorigenesis by establishing a cell-autonomous Hh signaling axis. ..

Research Grants30

  1. Regulation of Tumorigenesis and therapeutic resistance by Nrf2 in lung cancer
    Shyam Biswal; Fiscal Year: 2013
    ..Successful completion of this project will develop a new therapeutic strategy for lung cancer treatment. ..
  2. PROTON RADIATION THERAPY RESEARCH
    Thomas F DeLaney; Fiscal Year: 2013
    ..abstract_text> ..
  3. Wisconsin Center of Excellence in Genomics Science
    Michael Olivier; Fiscal Year: 2013
    ..Data, technology, and software will be widely disseminated by multiple mechanisms including licensing and commercialization activities. ..
  4. CELLULAR AND MOLECULAR MECHANISMS OF GASTROINTESTINAL CANCERS
    Lopa Mishra; Fiscal Year: 2013
    ..Significantly, this program promises to yield new therapies targeted at these difficult-to-treat lethal cancers at the bench, and then to translate the results rapidly into clinical care, at the bedside. ..
  5. Myofibroblasts in Gastrointestinal Cancers
    TIMOTHY CRAGIN WANG; Fiscal Year: 2013
    ..The three projects are highly translational with heavy use of human tissues and physiological mouse models of digestive cancers, and are linked to a Phase 1 clinical trial in human patients with pancreatic cancer. ..
  6. SPORE IN BREAST CANCER
    HENRY SHELTON EARP; Fiscal Year: 2013
    ..abstract_text> ..
  7. University of Maryland Greenebaum Cancer Center Support Grant
    Kevin J Cullen; Fiscal Year: 2013
    ..Reflecting our remarkable and continued growth, UMGCC seeks to renew its CCSG to enhance and expand its efforts in high-quality and clinically relevant cancer research. ..
  8. THERAPY OF LYMPHOMA/LEUKEMIA WITH MONOCLONAL ANTIBODIES
    Oliver W Press; Fiscal Year: 2013
    ..We anticipate that the investigations described in this application will allow us to maximize the therapeutic efficacy and minimize the toxicity of myeloablative RIT for hematologic malignancies. ..
  9. Optical Technologies and Molecular Imaging for Cervical Neoplasia
    Michele Follen; Fiscal Year: 2013
    ..abstract_text> ..
  10. HuR Targeted Nanotherapy for Lung Cancer
    Rajagopal Ramesh; Fiscal Year: 2013
    ..Aim 3: Determine the efficacy of HuR-TfNPs treatment in combination with small molecule inhibitors in vitro and in vivo. The outcome of our studies will result in advanced preclinical testing and translation to the clinic. ..
  11. The role of PKD3 in prostate carcinogenesis
    Qiming Jane Wang; Fiscal Year: 2013
    ..Fundamental new knowledge will be obtained concerning mechanisms of prostate oncogenesis thereby facilitating future design of novel treatment strategies to limit or prevent this deadly disease. ..
  12. Role of Transcriptional Corepressor CtBP1 in Prostate Cancer Progression
    Sooryanarayana Varambally; Fiscal Year: 2013
    ....
  13. Role and mechanism of action of p62/Sqstm1 in Ras-induced tumorigenesis in lung
    Jorge Moscat; Fiscal Year: 2013
    ..abstract_text> ..
  14. Role of Foxm1 in Lung Cancer Microenvironment
    TANYA KALIN; Fiscal Year: 2013
    ..Completion of the proposed studies will enable us to determine whether Foxm1 plays critical role in tumor microenvironment and whether Foxm1 is an important target for lung cancer treatment. ..
  15. Model-based predictions of responses RTK Pathway therapies
    Joe W Gray; Fiscal Year: 2013
    ..abstract_text> ..
  16. MutT Homolog 1 as a Novel Mediator of RAS Oncogene-Induced Pro-Malignant Pathways
    Priyamvada Rai; Fiscal Year: 2013
    ....
  17. Translational phosphoproteomics for lung cancer
    Scott A Gerber; Fiscal Year: 2013
    ....
  18. SPORE in Soft Tissue Sarcoma
    Samuel Singer; Fiscal Year: 2013
    ..abstract_text> ..
  19. Dissection of microRNA-21s role in non-small cell lung cancer
    MARK EDWARD HATLEY; Fiscal Year: 2013
    ..This environment will provide the ideal interdisciplinary setting not only to conduct the proposed experiments but to develop as an independent clinician scientist from which an academic career can be constructed. ..