The inhibition of SRC family kinase suppresses pancreatic cancer cell proliferation, migration, and invasion.

Abstract

OBJECTIVES:

Src is considered a rising therapeutic target for the treatment of solid tumors, and Src family kinases (SFKs) participate in cancer cell proliferation and survival. The role of SFK suppression was investigated in the proliferation, migration, and invasion of pancreatic cancer cells.

METHODS:

Knockdown of the SFKs in pancreatic cancer cells was achieved by transfecting small interfering RNAs, and its effects were investigated using proliferation, wound, and invasion assays.

RESULTS:

The SFK inhibitors suppressed proliferation and induced cell cycle arrest in pancreatic cancer cells. The SFK messenger RNA profiles showed that Yes1, Lyn, Fyn, Frk, Hck, and Src were expressed. Specific small interfering RNA transfection suppressed the messenger RNA expressions of Yes1, Lyn, Fyn, Frk, and Src, and the knockdown suppressed cell proliferation by 16.7% to 47.3% in PANC-1 cells. Knockdown of any of these 5 SFKs suppressed proliferation in other pancreatic cancer cell lines by 3.0% to 40.5%. The knockdowns significantly reduced pancreatic cancer cell migration by 24.9% to 66.7% and completely inhibited invasion.

CONCLUSIONS:

These results suggest that the knockdown of Yes1, Lyn, Fyn, Frk, or Src reduce human pancreatic cancer cell proliferation, migration, and invasion, and that SFKs should be viewed as critical therapeutic targets of pancreatic cancer.

• Authors: Dong Wook Je, Young Moon O, Young Geon Ji, Yunkyung Cho, Dong Hyeon Lee
• Journal: Pancreas (Pancreas) Vol. 43 Issue 5 Pg. 768-76 (Jul 2014) ISSN: 1536-4828 [Electronic] United States
• PMID: 24763074 (Publication Type: Journal Article)

Chemical References

• A 419259
• AG 1879
• Neoplasm Proteins
• Pyrimidines
• Pyrroles
• Protein-Tyrosine Kinases
• FRK protein, human
• FYN protein, human
• HCK protein, human
• Proto-Oncogene Proteins c-fyn
• Proto-Oncogene Proteins c-hck
• Proto-Oncogene Proteins c-yes
• Proto-Oncogene Proteins pp60(c-src)
• YES1 protein, human
• lyn protein-tyrosine kinase
• src-Family Kinases

Topics

• Blotting, Western
• Cell Cycle (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Humans
• Neoplasm Invasiveness
• Neoplasm Proteins (antagonists & inhibitors, genetics, metabolism)
• Pancreatic Neoplasms (genetics, metabolism, pathology)
• Protein-Tyrosine Kinases (antagonists & inhibitors, genetics, metabolism)
• Proto-Oncogene Proteins c-fyn (antagonists & inhibitors, genetics, metabolism)
• Proto-Oncogene Proteins c-hck (antagonists & inhibitors, genetics, metabolism)
• Proto-Oncogene Proteins c-yes (antagonists & inhibitors, genetics, metabolism)
• Proto-Oncogene Proteins pp60(c-src) (antagonists & inhibitors)
• Pyrimidines (pharmacology)
• Pyrroles (pharmacology)
• RNA Interference
• Reverse Transcriptase Polymerase Chain Reaction
• src-Family Kinases (antagonists & inhibitors, genetics, metabolism)