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.
According to the authors, in their previous study, they found that blockade of stromal-derived factor-1 (SDF-1)/ C-X-C chemokine receptor type 4 (CXCR4) signaling inhibits pancreatic cancer cell migration and invasion in vitro. However, the mechanism governing the downstream regulation of stromal-derived factor-1/C-X-C chemokine receptor type 4-mediated invasion remains unclear. 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 effectively inhibited by Smoothened inhibitor cyclopamine and siRNA specific 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. “Collaborating with Ma, we together would like to find better cancer therapeutics and elucidate the mechanisms of the targeted therapy for pancreatic cancer, one of the most lethal malignancies,” Wu said.
Cancer Letters is an international journal that considers full-length articles and mini reviews in the broad area of basic and translational oncology.
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