Faculty Collaboration Database

Overexpression of receptor tyrosine kinase Axl promotes tumor cell invasion and survival in pancreatic ductal adenocarcinoma. Cancer 2011 Feb 15;117(4):734-43

Date

10/06/2010

Pubmed ID

20922806

Pubmed Central ID

PMC4403266

DOI

10.1002/cncr.25483

Scopus ID

2-s2.0-79551709511 (requires institutional sign-in at Scopus site)   118 Citations

Abstract

BACKGROUND: The receptor tyrosine kinase Axl has been reported to be overexpressed in a variety of human cancers. Although previous studies have identified the role of Axl in the transformation, proliferation, survival, and invasion in cancers, the expression and functions of Axl in pancreatic cancer have not been studied in detail.

METHODS: The expression of Axl protein in 12 pancreatic cancer cell lines and 54 patient samples of stage II pancreatic ductal adenocarcinoma (PDA) and their paired non-neoplastic pancreatic tissue samples were examined. Using univariate and multivariate analysis, Axl expression was correlated with survival and other clinicopathologic features. To examine Axl functions in PDA, the effects of Axl knockdown on the invasion ability and radiation-induced apoptosis in PDA cell lines were measured.

RESULTS: Axl was overexpressed in 38 of 54 (70%) stage II PDA samples and 9 of 12 (75%) PDA cell lines. Axl overexpression was associated with higher frequencies of distant metastasis and poor overall and recurrence-free survivals (P = .03 and P = .04, respectively) independent of tumor size and stage or lymph node status in patients with stage II PDA. Knockdown of Axl expression in PDA cells abolished Gas6-mediated Akt activation, decreased invasion, and increased radiation-induced PARP cleavage and the percentage of apoptosis.

CONCLUSIONS: This study showed that Gas6 and Axl are frequently overexpressed in PDA cells and are associated with a poor prognosis in patients with stage II PDA. Axl promotes the invasion and survival of PDA cells. Therefore, targeting the Axl signaling pathway may represent a new approach to the treatment of PDA.

Author List

Song X, Wang H, Logsdon CD, Rashid A, Fleming JB, Abbruzzese JL, Gomez HF, Evans DB, Wang H

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Aged
Carcinoma, Pancreatic Ductal
Cell Line, Tumor
Female
Humans
Intercellular Signaling Peptides and Proteins
Male
Middle Aged
Neoplasm Invasiveness
Pancreatic Neoplasms
Prognosis
Proto-Oncogene Proteins
RNA, Small Interfering
Receptor Protein-Tyrosine Kinases
Up-Regulation