JOURNAL ARTICLE

Beta-catenin is a promising key factor in the SDF-1/CXCR4 axis on metastasis of pancreatic cancer

Zheng Wang, Qingyong Ma
Medical Hypotheses 2007, 69 (4): 816-20
17379424
Metastasis is recently the most fearsome of cancer. Pancreatic cancer is the fourth leading cause of cancer death. Morbidity and mortality from pancreatic cancer is conspicuously associated with metastasis. However, the mechanism of metastasis is not well described. Early studies mostly focus on the "soil and seed" hypothesis. Recently, the chemotaxis hypothesis has been paid more attention. Cancer cell with high expression of chemokine receptor will spread to the specific sites where the ligand is highly secreted. It has been demonstrated that SDF-1/CXCR4 signaling, one of the most important chemokine receptor-ligand complexes, was considered to play a critical role in pancreatic cancer organ-specific metastasis through some possible pathways. However, studies do not clarify the mechanism of SDF-1/CXCR4 signaling on pancreatic cancer progression. Beta-catenin, an important factor in canonical Wnt signaling pathway, also makes great contributions on cancer invasion and metastasis. It seems that Wnt/beta-catenin has a significant role in pancreatic cancer progression through interactions with different protein complexes. In the previous study of neural development, the relationship between SDF-1/CXCR4 signaling and beta-catenin has been described. It gave a clue to describe the correlation between SDF-1/CXCR4 signaling and Wnt/beta-catenin pathway. According to this, we postulate that beta-catenin is a promising key factor of SDF-1/CXCR4 signaling to regulate the metastasis of pancreatic cancer. With the stimulation of SDF-1 on highly metastatic pancreatic cancer cells, beta-catenin will separate from different complexes, translocate into the nucleus, trigger the expression of target genes and finally promote the migration of pancreatic cancer cells to specific sites. Through the observation of this crosstalk, it is possible to understand more clearly about the pancreatic cancer specific metastasis and to make some contributions on gene therapy of pancreatic cancer.

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