Fargo, N.D. – Erxi Wu, assistant professor of pharmaceutical sciences; Kruttika Bhat, doctoral student in the Wu lab; and Fengfei Wang, research associate in pharmaceutical sciences, co-wrote the article, “SDF-1/CXCR4 signaling induces pancreatic cancer cell invasion and epithelial-mesenchymal transition in vitro through non-canonical activation of Hedgehog pathway,” which will be published by Cancer Letters.

In this current project, they report the role of stromal-derived factor-1/C-X-C chemokine receptor type 4 in pancreatic cancer and the possible mechanism of stromal-derived factor-1/C-X-C chemokine receptor type 4-mediated pancreatic cancer invasion. They show that there is a cross talk between stromal-derived factor-1/C-X-C chemokine receptor type 4 axis and non-canonical Hedgehog pathway in pancreatic cancer. Furthermore, their data demonstrate that the ligand of C-X-C chemokine receptor type 4, stromal-derived factor-1 induces C-X-C chemokine receptor type 4-positive pancreatic cancer invasion, epithelial-mesenchymal transition process and activates the non-canonical Hedgehog pathway. Moreover, they also demonstrate that the invasion of a pancreatic cancer and EMT resulting from the activation of stromal-derived factor-1/C-X-C chemokine receptor type 4 axis is selectively  inhibited by Smoothened inhibitor cyclopamine and siRNA specificc to Gli-1.

“Collectively, these data demonstrate that stromal-derived factor- 1/C-X-C chemokine receptor type 4 modulates the non-canonical Hedgehog pathway by increasing the transcription of Smoothened in a ligand-independent manner. Taken together, stromal-derived factor-1/C-X-C chemokine receptor type 4 axis may represent a promising therapeutic target to prevent pancreatic cancer progression,” Wu said.

The paper was co-written with Qingyong Ma lab at Xi’an Jiaotong University, China.