Identification of Pancreatic Cancer Metastasis Associated Genes by in Vivo Genome-wide RNAi Screening
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AbstractBackground: Pancreatic cancer is an aggressive malignancy with extremely poor prognosis. It is usually diagnosed when metastases are already present. To identify genes that play critical roles in the processes of pancreatic cancer metastasis, a whole genome RNAi screening was performed.

Materials & Methods: An shRNA library targeting all human genes was introduced into a human pancreatic cancer cell line capan-2. The infected cells were then transplanted into the pancreas of nude mice. Because capan-2 is of low metastatic potential, we hypothesized that knocking down of metastasis suppressor genes would facilitate capan-2 cells to spread to the liver. By retrieving shRNA templates from the liver metastatic nodules, several candidate genes were found. One of them, SOX9, has been validated as metastasis suppressor gene in vivo, implying that loss of expression of SOX9 promotes pancreatic cancer metastasis.

Results: Our genome wide RNAi screening identified SOX9 as a metastasis suppressor gene in pancreatic cancer. In the validation experiments, 10 and 11 nude mice were used for control shCtrl group and shSOX9 group respectively. All of them had primary tumors established. 7 out of 11 mice in shSOX9 group developed liver metastasis, whereas only 2 out of 10 metastasized in control group. Knocking-down of SOX9 promoted the orthotopically transplanted capan-2 cells to metastasize to the liver.

Conclusions: SOX9 might play a role in tumor metastasis in pancreatic cancer.
All Author(s) ListCHEN Yangchao
Name of ConferenceThe 11th International Conference on Genomics
Start Date of Conference04/11/2016
End Date of Conference06/11/2016
Place of ConferenceShenzhen
Country/Region of ConferenceChina
Place of PublicationShenzhen
LanguagesEnglish-United States

Last updated on 2018-23-01 at 04:41