Focal overexpression of CEACAM6 contributes to enhanced tumourigenesis in head and neck cancer via suppression of apoptosis

Cameron, Sarina, de Long, Lilia Merida, Hazar-Rethinam, Mehlika, Topkas, Eleni, Endo-Munoz, Liliana, Cumming, Andrew, Gannon, Orla, Guminski, Alexander and Saunders, Nicholas (2012) Focal overexpression of CEACAM6 contributes to enhanced tumourigenesis in head and neck cancer via suppression of apoptosis. Molecular Cancer, 11 74.1-74.11. doi:10.1186/1476-4598-11-74


Author Cameron, Sarina
de Long, Lilia Merida
Hazar-Rethinam, Mehlika
Topkas, Eleni
Endo-Munoz, Liliana
Cumming, Andrew
Gannon, Orla
Guminski, Alexander
Saunders, Nicholas
Total Author Count Override 9
Title Focal overexpression of CEACAM6 contributes to enhanced tumourigenesis in head and neck cancer via suppression of apoptosis
Journal name Molecular Cancer   Check publisher's open access policy
ISSN 1476-4598
Publication date 2012-09
Sub-type Article (original research)
DOI 10.1186/1476-4598-11-74
Open Access Status DOI
Volume 11
Start page 74.1
End page 74.11
Total pages 11
Place of publication London, United Kingdom
Publisher BioMed Centra
Collection year 2013
Language eng
Formatted abstract
Background: Overexpression of CEACAM6 has been reported for a number of malignancies. However, the mechanism of how CEACAM6 contributes to cancer formation and its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. Therefore, we examined the role of CEACAM6 in head and neck squamous cell carcinoma (HNSCC).

Methods: CEACAM6 expression was examined in normal squamous epithelia as well as a number of patient HNSCC samples and tumours derived from HNSCC cell lines injected into NOD/SCID mice. CEACAM6 expression was manipulated in HNSCC cell lines by shRNA-mediated CEACAM6 knockdown or virally-delivered overexpression of CEACAM6. The role of CEACAM6 in tumour growth and chemotherapeutic sensitivity was then assessed in vivo and in vitro respectively.

Results:
CEACAM6 expression was significantly increased in highly tumourigenic HNSCC cell lines when compared to poorly tumourigenic HNSCC cell lines. Moreover, HNSCC patient tumours demonstrated focal expression of CEACAM6. Functional investigation of CEACAM6, involving over-expression and knock down studies, demonstrated that CEACAM6 over-expression could enhance tumour initiating activity and tumour growth via activation of AKT and suppression of caspase-3 mediated cell death.

Conclusion: We report that CEACAM6 is focally overexpressed in a large fraction of human HNSCCs in situ. We also show that over-expression of CEACAM6 increases tumour growth and tumour initiating activity by suppressing PI3K/AKT-dependent apoptosis of HNSCC in a xenotransplant model of HNSCC. Finally, our studies indicate that foci of CEACAM6 expressing cells are selectively ablated by treatment of xenotransplant tumours with pharmacological inhibitors of PI3K/AKT in vivo.
Keyword Ceacam6
Hnscc
Tumour initiation
Cleaved Caspase 3
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article number 74

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
UQ Diamantina Institute Publications
 
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