| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
Departments of 1 Otolaryngology, 2 Pharmacology, and 3 Molecular Genetics and Biochemistry, 4 University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; and 5 Abbott Bioresearch Center, Worcester, Massachusetts
Head and neck squamous cell carcinomas (HNSCCs) are characterized by up-regulation of the epidermal growth factor receptor (EGFR). We previously reported that a gastrin-releasing peptide/gastrin-releasing peptide receptor (GRP/GRPR) autocrine growth pathway is activated early in HNSCC carcinogenesis. GRP can induce rapid phosphorylation of EGFR and p42/44 mitogen-activated protein kinase (MAPK) activation in part via extracellular release of transforming growth factor 
(TGF-) by matrix metalloproteinases (MMPs). It has been reported that Src family kinases are activated by G-protein–coupled receptors (GPCRs), followed by downstream EGFR and MAPK activation. To further elucidate the mechanism of activation of EGFR by GRP in HNSCC, we investigated the role of Src family kinases. Blockade of Src family kinases using an Src-specific tyrosine kinase inhibitor A-419259 decreased GRP-induced EGFR phosphorylation and MAPK activation. GRP also failed to induce MAPK activation in dominant-negative c-Src–transfected HNSCC cells. Invasion and growth assays showed that c-Src was required for GRP-induced proliferation or invasion of HNSCC cells. In addition to TGF- release, GRP induced amphiregulin, but not EGF, secretion into HNSCC cell culture medium, an effect that was blocked by the MMP inhibitor marimastat. TGF- and amphiregulin secretion by GRP stimulation also was inhibited by blockade of Src family kinases. These results suggest that Src family kinases contribute to GRP-mediated EGFR growth and invasion pathways by facilitating cleavage and release of TGF- and amphiregulin in HNSCC.
This article has been cited by other articles:
|
|
 |
|
  A. M. Egloff, M. E. Rothstein, R. Seethala, J. M. Siegfried, J. R. Grandis, and L. P. Stabile Cross-Talk between Estrogen Receptor and Epidermal Growth Factor Receptor in Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., November 1, 2009; 15(21): 6529 - 6540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Gilmore, R. M. Gonterman, K. Menon, G. Lorch, D. J. Riese II, A. Robling, and J. Foley Reconstitution of Amphiregulin-Epidermal Growth Factor Receptor Signaling in Lung Squamous Cell Carcinomas Activates PTHrP Gene Expression and Contributes to Cancer-Mediated Diseases of the Bone Mol. Cancer Res., October 1, 2009; 7(10): 1714 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. V. Lu, S. Zhu, A. Cvrljevic, T. T. Huang, S. Sarkaria, D. Ahkavan, J. Dang, E. B. Dinca, S. B. Plaisier, I. Oderberg, et al. Fyn and Src Are Effectors of Oncogenic Epidermal Growth Factor Receptor Signaling in Glioblastoma Patients Cancer Res., September 1, 2009; 69(17): 6889 - 6898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zou, S. M. Thomas, Z.-W. Yan, J. R. Grandis, A. Vogt, and L.-Y. Li Human rhomboid family-1 gene RHBDF1 participates in GPCR-mediated transactivation of EGFR growth signals in head and neck squamous cancer cells FASEB J, February 1, 2009; 23(2): 425 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wang, V. Patel, H. Miyazaki, J.S. Gutkind, and W.A. Yeudall Role for EPS8 in squamous carcinogenesis Carcinogenesis, January 1, 2009; 30(1): 165 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Misawa, Y. Ueda, T. Kanazawa, Y. Misawa, I. Jang, J. C. Brenner, T. Ogawa, S. Takebayashi, R. A. Grenman, J. G. Herman, et al. Epigenetic Inactivation of Galanin Receptor 1 in Head and Neck Cancer Clin. Cancer Res., December 1, 2008; 14(23): 7604 - 7613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Rodland, N. Bollinger, D. Ippolito, L. K. Opresko, R. J. Coffey, R. Zangar, and H. S. Wiley Multiple Mechanisms Are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells J. Biol. Chem., November 14, 2008; 283(46): 31477 - 31487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Lehnerdt, P. Franz, A. Bankfalvi, S. Grehl, K. Jahnke, S. Lang, K. W. Schmid, W. Siffert, and U. H. Frey Association Study of the G-Protein {beta}3 Subunit C825T Polymorphism with Disease Progression an Overall Survival in Patients with Head and Neck Squamous Cell Carcinoma Cancer Epidemiol. Biomarkers Prev., November 1, 2008; 17(11): 3203 - 3207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Block and J. K. Klarlund Wounding Sheets of Epithelial Cells Activates the Epidermal Growth Factor Receptor through Distinct Short- and Long-Range Mechanisms Mol. Biol. Cell, November 1, 2008; 19(11): 4909 - 4917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Koppikar, S.-H. Choi, A. M. Egloff, Q. Cai, S. Suzuki, M. Freilino, H. Nozawa, S. M. Thomas, W. E. Gooding, J. M. Siegfried, et al. Combined Inhibition of c-Src and Epidermal Growth Factor Receptor Abrogates Growth and Invasion of Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., July 1, 2008; 14(13): 4284 - 4291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Nozawa, G. Howell, S. Suzuki, Q. Zhang, Y. Qi, J. Klein-Seetharaman, A. Wells, J. R. Grandis, and S. M. Thomas Combined Inhibition of PLC{gamma}-1 and c-Src Abrogates Epidermal Growth Factor Receptor-Mediated Head and Neck Squamous Cell Carcinoma Invasion Clin. Cancer Res., July 1, 2008; 14(13): 4336 - 4344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Seethala, W. E. Gooding, P. N. Handler, B. Collins, Q. Zhang, J. M. Siegfried, and J. R. Grandis Immunohistochemical Analysis of Phosphotyrosine Signal Transducer and Activator of Transcription 3 and Epidermal Growth Factor Receptor Autocrine Signaling Pathways in Head and Neck Cancers and Metastatic Lymph Nodes Clin. Cancer Res., March 1, 2008; 14(5): 1303 - 1309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Thomas, M. J. Ogagan, M. L. Freilino, S. Strychor, D. R. Walsh, W. E. Gooding, J. R. Grandis, and W. C. Zamboni Antitumor Mechanisms of Systemically Administered Epidermal Growth Factor Receptor Antisense Oligonucleotides in Combination with Docetaxel in Squamous Cell Carcinoma of the Head and Neck Mol. Pharmacol., March 1, 2008; 73(3): 627 - 638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. D. Ardizzone, X. Zhan, B. P. Ander, and F. R. Sharp Src Kinase Inhibition Improves Acute Outcomes After Experimental Intracerebral Hemorrhage Stroke, May 1, 2007; 38(5): 1621 - 1625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K.S. Ku, D. C. Nguyen, M. Karaman, P. Gill, J. G. Hacia, and D. L. Crowe Loss of p53 Expression Correlates with Metastatic Phenotype and Transcriptional Profile in a New Mouse Model of Head and Neck Cancer Mol. Cancer Res., April 1, 2007; 5(4): 351 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Zhang, N. E. Bhola, V. W. Y. Lui, D. R. Siwak, S. M. Thomas, C. T. Gubish, J. M. Siegfried, G. B. Mills, D. Shin, and J. R. Grandis Antitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer Mol. Cancer Ther., April 1, 2007; 6(4): 1414 - 1424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, S. Kalyankrishna, M. Wislez, N. Thilaganathan, B. Saigal, W. Wei, L. Ma, I. I. Wistuba, F. M. Johnson, and J. M. Kurie Src-Family Kinases Are Activated in Non-Small Cell Lung Cancer and Promote the Survival of Epidermal Growth Factor Receptor-Dependent Cell Lines Am. J. Pathol., January 1, 2007; 170(1): 366 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Thomas, N. E. Bhola, Q. Zhang, S. C. Contrucci, A. L. Wentzel, M. L. Freilino, W. E. Gooding, J. M. Siegfried, D. C. Chan, and J. R. Grandis Cross-talk between G Protein-Coupled Receptor and Epidermal Growth Factor Receptor Signaling Pathways Contributes to Growth and Invasion of Head and Neck Squamous Cell Carcinoma Cancer Res., December 15, 2006; 66(24): 11831 - 11839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Yamamoto, G. Mammadova, R. X.-D. Song, Y. Fukami, and K.-i. Sato Tyrosine phosphorylation of p145met mediated by EGFR and Src is required for serum-independent survival of human bladder carcinoma cells J. Cell Sci., November 15, 2006; 119(22): 4623 - 4633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, Y. Shao, J. J. Voorhees, and G. J. Fisher Oxidative Inhibition of Receptor-type Protein-tyrosine Phosphatase {kappa} by Ultraviolet Irradiation Activates Epidermal Growth Factor Receptor in Human Keratinocytes J. Biol. Chem., September 15, 2006; 281(37): 27389 - 27397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. V. Mukhin, M. Gooz, J. R. Raymond, and M. N. Garnovskaya Collagenase-2 and -3 Mediate Epidermal Growth Factor Receptor Transactivation by Bradykinin B2 Receptor in Kidney Cells J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1033 - 1043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Rothschild, A. H. Shim, A. G. Ammer, L. C. Kelley, K. B. Irby, J. A. Head, L. Chen, M. Varella-Garcia, P. G. Sacks, B. Frederick, et al. Cortactin Overexpression Regulates Actin-Related Protein 2/3 Complex Activity, Motility, and Invasion in Carcinomas with Chromosome 11q13 Amplification Cancer Res., August 15, 2006; 66(16): 8017 - 8025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhao, D. He, B. Saatian, T. Watkins, E. Wm. Spannhake, N. J. Pyne, and V. Natarajan Regulation of Lysophosphatidic Acid-induced Epidermal Growth Factor Receptor Transactivation and Interleukin-8 Secretion in Human Bronchial Epithelial Cells by Protein Kinase C{delta}, Lyn Kinase, and Matrix Metalloproteinases J. Biol. Chem., July 14, 2006; 281(28): 19501 - 19511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kalyankrishna and J. R. Grandis Epidermal Growth Factor Receptor Biology in Head and Neck Cancer J. Clin. Oncol., June 10, 2006; 24(17): 2666 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Zhang, S. M. Thomas, V. W. Y. Lui, S. Xi, J. M. Siegfried, H. Fan, T. E. Smithgall, G. B. Mills, and J. R. Grandis Phosphorylation of TNF-{alpha} converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation PNAS, May 2, 2006; 103(18): 6901 - 6906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Knowlden, I. R. Hutcheson, D. Barrow, J. M. W. Gee, and R. I. Nicholson Insulin-Like Growth Factor-I Receptor Signaling in Tamoxifen-Resistant Breast Cancer: A Supporting Role to the Epidermal Growth Factor Receptor Endocrinology, November 1, 2005; 146(11): 4609 - 4618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Adjei and M. Hidalgo Intracellular Signal Transduction Pathway Proteins As Targets for Cancer Therapy J. Clin. Oncol., August 10, 2005; 23(23): 5386 - 5403. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
