Skip to main content
Top
Published in: BMC Cancer 1/2012

Open Access 01-12-2012 | Research article

Opposing function of MYBBP1A in proliferation and migration of head and neck squamous cell carcinoma cells

Authors: Gustavo A Acuña Sanhueza, Leonie Faller, Babitha George, Jennifer Koffler, Vinko Misetic, Christa Flechtenmacher, Gerhard Dyckhoff, Peter P Plinkert, Peter Angel, Christian Simon, Jochen Hess

Published in: BMC Cancer | Issue 1/2012

Login to get access

Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent and lethal cancers worldwide and mortality mostly results from loco-regional recurrence and metastasis. Despite its significance, our knowledge on molecular, cellular and environmental mechanisms that drive disease pathogenesis remains largely elusive, and there are limited therapeutic options, with only negligible clinical benefit.

Methods

We applied global gene expression profiling with samples derived from a recently established mouse model for oral cancer recurrence and identified a list of genes with differential expression between primary and recurrent tumors.

Results

One differentially expressed gene codes for Myb-binding protein 1a (MYBBP1A), which is known as a transcriptional co-regulator that physically interacts with nuclear transcription factors, such as NFκB and p53. We confirmed significantly reduced MYBBP1A protein levels on tissue sections of recurrent mouse tumors compared to primary tumors by immunohistochemistry, and found aberrant MYBBP1A protein levels also in tumor samples of HNSCC patients. Interestingly, silencing of MYBBP1A expression in murine SCC7 and in human HNSCC cell lines elicited increased migration but decreased cell growth.

Conclusion

We provide experimental evidence that MYBBP1A is an important molecular switch in the regulation of tumor cell proliferation versus migration in HNSCC and it will be a major challenge for the future to proof the concept whether regulation MYBBP1A expression and/or function could serve as a novel option for anti-cancer therapy.
Appendix
Available only for authorised users
Literature
1.
go back to reference Argiris A, Karamouzis MV, Raben D, Ferris RL: Head and neck cancer. Lancet. 2008, 371: 1695-1709. 10.1016/S0140-6736(08)60728-X.CrossRefPubMed Argiris A, Karamouzis MV, Raben D, Ferris RL: Head and neck cancer. Lancet. 2008, 371: 1695-1709. 10.1016/S0140-6736(08)60728-X.CrossRefPubMed
2.
go back to reference Leemans C, Braakhuis B, Brakenhoff R: The molecular biology of head and neck cancer. Nat Rev Cancer. 2011, 11: 9-22. 10.1038/nrc2982.CrossRefPubMed Leemans C, Braakhuis B, Brakenhoff R: The molecular biology of head and neck cancer. Nat Rev Cancer. 2011, 11: 9-22. 10.1038/nrc2982.CrossRefPubMed
3.
go back to reference Forastiere A, Koch W, Trotti A, Sidransky D: Head and neck cancer. N Engl J Med. 2001, 345: 1890-1900. 10.1056/NEJMra001375.CrossRefPubMed Forastiere A, Koch W, Trotti A, Sidransky D: Head and neck cancer. N Engl J Med. 2001, 345: 1890-1900. 10.1056/NEJMra001375.CrossRefPubMed
4.
go back to reference Hunter KD, Parkinson EK, Harrison PR: Profiling early head and neck cancer. Nat Rev Cancer. 2005, 5: 127-135. 10.1038/nrc1549.CrossRefPubMed Hunter KD, Parkinson EK, Harrison PR: Profiling early head and neck cancer. Nat Rev Cancer. 2005, 5: 127-135. 10.1038/nrc1549.CrossRefPubMed
5.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T: Cancer statistics. CA Cancer J Clin. 2008, 58: 71-96. 10.3322/CA.2007.0010.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T: Cancer statistics. CA Cancer J Clin. 2008, 58: 71-96. 10.3322/CA.2007.0010.CrossRefPubMed
6.
go back to reference Thomas GR, Nadiminti H, Regalado J: Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma. Int J Exp Pathol. 2005, 86: 347-363. 10.1111/j.0959-9673.2005.00447.x.CrossRefPubMedPubMedCentral Thomas GR, Nadiminti H, Regalado J: Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma. Int J Exp Pathol. 2005, 86: 347-363. 10.1111/j.0959-9673.2005.00447.x.CrossRefPubMedPubMedCentral
7.
go back to reference Smith LP, Thomas GR: Animal models for the study of squamous cell carcinoma of the upper aerodigestive tract: a historical perspective with review of their utility and limitations. Part A. Chemically-induced de novo cancer, syngeneic animal models of HNSCC, animal models of transplanted xenogeneic human tumors. Int J Cancer. 2006, 118: 2111-2122. 10.1002/ijc.21694.CrossRefPubMed Smith LP, Thomas GR: Animal models for the study of squamous cell carcinoma of the upper aerodigestive tract: a historical perspective with review of their utility and limitations. Part A. Chemically-induced de novo cancer, syngeneic animal models of HNSCC, animal models of transplanted xenogeneic human tumors. Int J Cancer. 2006, 118: 2111-2122. 10.1002/ijc.21694.CrossRefPubMed
8.
go back to reference Behren A, Kamenisch Y, Muehlen S, Flechtenmacher C, Haberkorn U, Hilber H: Development of an oral cancer recurrence mouse model after surgical resection. Int J Oncol. 2010, 36: 849-855.PubMed Behren A, Kamenisch Y, Muehlen S, Flechtenmacher C, Haberkorn U, Hilber H: Development of an oral cancer recurrence mouse model after surgical resection. Int J Oncol. 2010, 36: 849-855.PubMed
9.
go back to reference Favier D, Gonda TJ: Detection of proteins that bind to the leucine zipper motif of c-Myb. Oncogene. 1994, 9: 305-311.PubMed Favier D, Gonda TJ: Detection of proteins that bind to the leucine zipper motif of c-Myb. Oncogene. 1994, 9: 305-311.PubMed
10.
go back to reference Tavner FJ, Simpson R, Tashiro S, Favier D, Jenkins NA, Gilbert DJ: Molecular cloning reveals that the p160 Myb-binding protein is a novel, predominantly nucleolar protein which may play a role in transactivation by Myb. Mol Cell Biol. 1998, 18: 989-1002.CrossRefPubMedPubMedCentral Tavner FJ, Simpson R, Tashiro S, Favier D, Jenkins NA, Gilbert DJ: Molecular cloning reveals that the p160 Myb-binding protein is a novel, predominantly nucleolar protein which may play a role in transactivation by Myb. Mol Cell Biol. 1998, 18: 989-1002.CrossRefPubMedPubMedCentral
11.
go back to reference Owen HR, Elser M, Cheung E, Gersbach M, Kraus WL, Hottiger MO: MYBBP1a is a novel repressor of NF-kappaB. J Mol Biol. 2007, 366: 725-736. 10.1016/j.jmb.2006.11.099.CrossRefPubMed Owen HR, Elser M, Cheung E, Gersbach M, Kraus WL, Hottiger MO: MYBBP1a is a novel repressor of NF-kappaB. J Mol Biol. 2007, 366: 725-736. 10.1016/j.jmb.2006.11.099.CrossRefPubMed
12.
go back to reference Roesch Ely M, Nees M, Karsai S, Magele I, Bogumil R, Vorderwulbecke S: Transcript and proteome analysis reveals reduced expression of calgranulins in head and neck squamous cell carcinoma. Eur J Cell Biol. 2005, 84: 431-444. 10.1016/j.ejcb.2005.01.003.CrossRefPubMed Roesch Ely M, Nees M, Karsai S, Magele I, Bogumil R, Vorderwulbecke S: Transcript and proteome analysis reveals reduced expression of calgranulins in head and neck squamous cell carcinoma. Eur J Cell Biol. 2005, 84: 431-444. 10.1016/j.ejcb.2005.01.003.CrossRefPubMed
13.
go back to reference Gebhardt C, Riehl A, Durchdewald M, Nemeth J, Furstenberger G, Muller-Decker K: RAGE signaling sustains inflammation and promotes tumor development. J Exp Med. 2008, 205: 275-285. 10.1084/jem.20070679.CrossRefPubMedPubMedCentral Gebhardt C, Riehl A, Durchdewald M, Nemeth J, Furstenberger G, Muller-Decker K: RAGE signaling sustains inflammation and promotes tumor development. J Exp Med. 2008, 205: 275-285. 10.1084/jem.20070679.CrossRefPubMedPubMedCentral
14.
go back to reference Hess J, Porte D, Munz C, Angel P: AP-1 and Cbfa/runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblast-specific element 2/AP-1 composite element. J Biol Chem. 2001, 2001 (276): 20029-20038.CrossRef Hess J, Porte D, Munz C, Angel P: AP-1 and Cbfa/runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblast-specific element 2/AP-1 composite element. J Biol Chem. 2001, 2001 (276): 20029-20038.CrossRef
15.
go back to reference Pettus JR, Johnson JJ, Shi Z, Davis JW, Koblinski J, Ghosh S: Multiple kallikrein (KLK 5, 7, 8, and 10) expression in squamous cell carcinoma of the oral cavity. Histol Histopathol. 2009, 24: 197-207.PubMedPubMedCentral Pettus JR, Johnson JJ, Shi Z, Davis JW, Koblinski J, Ghosh S: Multiple kallikrein (KLK 5, 7, 8, and 10) expression in squamous cell carcinoma of the oral cavity. Histol Histopathol. 2009, 24: 197-207.PubMedPubMedCentral
16.
go back to reference Borgono CA, Diamandis EP: The emerging roles of human tissue kallikreins in cancer. Nat Rev Cancer. 2004, 4: 876-890. 10.1038/nrc1474.CrossRefPubMed Borgono CA, Diamandis EP: The emerging roles of human tissue kallikreins in cancer. Nat Rev Cancer. 2004, 4: 876-890. 10.1038/nrc1474.CrossRefPubMed
17.
go back to reference Sharma B, Sriram G, Saraswathi TR, Sivapathasundharam B: Immunohistochemical evaluation of mast cells and angiogenesis in oral squamous cell carcinoma. Indian J Dent Res. 2010, 21: 260-265. 10.4103/0970-9290.66655.CrossRefPubMed Sharma B, Sriram G, Saraswathi TR, Sivapathasundharam B: Immunohistochemical evaluation of mast cells and angiogenesis in oral squamous cell carcinoma. Indian J Dent Res. 2010, 21: 260-265. 10.4103/0970-9290.66655.CrossRefPubMed
18.
go back to reference Cheung ST, Leung KL, Ip YC, Chen X, Fong DY, Ng IO: Claudin-10 expression level is associated with recurrence of primary hepatocellular carcinoma. Clin Cancer Res. 2005, 11: 551-556.PubMed Cheung ST, Leung KL, Ip YC, Chen X, Fong DY, Ng IO: Claudin-10 expression level is associated with recurrence of primary hepatocellular carcinoma. Clin Cancer Res. 2005, 11: 551-556.PubMed
19.
go back to reference Wolf JS, Li G, Varadhachary A, Petrak K, Schneyer M, Li D: Oral lactoferrin results in T cell-dependent tumor inhibition of head and neck squamous cell carcinoma in vivo. Clin Cancer Res. 2007, 13: 1601-1610. 10.1158/1078-0432.CCR-06-2008.CrossRefPubMedPubMedCentral Wolf JS, Li G, Varadhachary A, Petrak K, Schneyer M, Li D: Oral lactoferrin results in T cell-dependent tumor inhibition of head and neck squamous cell carcinoma in vivo. Clin Cancer Res. 2007, 13: 1601-1610. 10.1158/1078-0432.CCR-06-2008.CrossRefPubMedPubMedCentral
20.
go back to reference Varadhachary A, Wolf JS, Petrak K, O'Malley BW, Spadaro M, Curcio C: Oral lactoferrin inhibits growth of established tumors and potentiates conventional chemotherapy. Int J Cancer. 2004, 111: 398-403. 10.1002/ijc.20271.CrossRefPubMed Varadhachary A, Wolf JS, Petrak K, O'Malley BW, Spadaro M, Curcio C: Oral lactoferrin inhibits growth of established tumors and potentiates conventional chemotherapy. Int J Cancer. 2004, 111: 398-403. 10.1002/ijc.20271.CrossRefPubMed
21.
go back to reference Yamauchi T, Keough RA, Gonda TJ, Ishii S: Ribosomal stress induces processing of Mybbp1a and its translocation from the nucleolus to the nucleoplasm. Genes Cells. 2008, 13: 27-39.CrossRefPubMed Yamauchi T, Keough RA, Gonda TJ, Ishii S: Ribosomal stress induces processing of Mybbp1a and its translocation from the nucleolus to the nucleoplasm. Genes Cells. 2008, 13: 27-39.CrossRefPubMed
22.
go back to reference Perrera C, Colombo R, Valsasina B, Carpinelli P, Troiani S, Modugno M: Identification of Myb-binding protein 1A (MYBBP1A) as a novel substrate for aurora B kinase. J Biol Chem. 2010, 285: 11775-11785. 10.1074/jbc.M109.068312.CrossRefPubMedPubMedCentral Perrera C, Colombo R, Valsasina B, Carpinelli P, Troiani S, Modugno M: Identification of Myb-binding protein 1A (MYBBP1A) as a novel substrate for aurora B kinase. J Biol Chem. 2010, 285: 11775-11785. 10.1074/jbc.M109.068312.CrossRefPubMedPubMedCentral
23.
go back to reference Tsuchiya M, Katagiri N, Kuroda T, Kishimoto H: Critical role of the nucleolus in activation of the p53-dependent postmitotic checkpoint. Biochem Biophys Res Commun. 2011, 407: 378-382. 10.1016/j.bbrc.2011.03.029.CrossRefPubMed Tsuchiya M, Katagiri N, Kuroda T, Kishimoto H: Critical role of the nucleolus in activation of the p53-dependent postmitotic checkpoint. Biochem Biophys Res Commun. 2011, 407: 378-382. 10.1016/j.bbrc.2011.03.029.CrossRefPubMed
24.
go back to reference Kuroda T, Murayama A, Katagiri N, Ohta Y, Fujita E, Masumoto H, Ema M, Takahashi S, Kimura K, Yanagisawa J: RNA content in the nucleolus alters p53 acetylation via MYBBP1A. EMBO J. 2011, 30: 1054-1066. 10.1038/emboj.2011.23.CrossRefPubMedPubMedCentral Kuroda T, Murayama A, Katagiri N, Ohta Y, Fujita E, Masumoto H, Ema M, Takahashi S, Kimura K, Yanagisawa J: RNA content in the nucleolus alters p53 acetylation via MYBBP1A. EMBO J. 2011, 30: 1054-1066. 10.1038/emboj.2011.23.CrossRefPubMedPubMedCentral
25.
go back to reference Molinolo A, Amornphimoltham P, Squarize CH, Castilho RM, Patel V, Gutkind JS: Dysregulated molecular networks in head and neck carcinogenesis. Oral Oncol. 2009, 45: 324-334. 10.1016/j.oraloncology.2008.07.011.CrossRefPubMed Molinolo A, Amornphimoltham P, Squarize CH, Castilho RM, Patel V, Gutkind JS: Dysregulated molecular networks in head and neck carcinogenesis. Oral Oncol. 2009, 45: 324-334. 10.1016/j.oraloncology.2008.07.011.CrossRefPubMed
26.
go back to reference Kuwabara T, Hiyama T, Tanaka S, Yoshihara M, Arihiro K, Chayama K: Genetic pathways of multiple esophageal squamous cell carcinomas. Onco Rep. 2011, 25: 453-459. Kuwabara T, Hiyama T, Tanaka S, Yoshihara M, Arihiro K, Chayama K: Genetic pathways of multiple esophageal squamous cell carcinomas. Onco Rep. 2011, 25: 453-459.
Metadata
Title
Opposing function of MYBBP1A in proliferation and migration of head and neck squamous cell carcinoma cells
Authors
Gustavo A Acuña Sanhueza
Leonie Faller
Babitha George
Jennifer Koffler
Vinko Misetic
Christa Flechtenmacher
Gerhard Dyckhoff
Peter P Plinkert
Peter Angel
Christian Simon
Jochen Hess
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-12-72

Other articles of this Issue 1/2012

BMC Cancer 1/2012 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine