Weight-adjusted dalteparin for prevention of vascular thromboembolism in advanced pancreatic cancer patients decreases serum tissue factor and serum-mediated induction of cancer cell invasion

Pancreatic cancer has a high mortality rate due to metastasis. Whereas KRAS is mutated in most pancreatic cancer patients, controlling KRAS or its downstream effectors has not been succeeded clinically. ARL4C is a small G protein whose expression is induced by the Wnt and EGF-RAS pathways. In the present study, we found that ARL4C is frequently overexpressed in pancreatic cancer patients and showed that its localization to invasive pseudopods is required for cancer cell invasion. IQGAP1 was identified as a novel interacting protein for ARL4C. ARL4C recruited IQGAP1 and its downstream effector, MMP14, to invasive pseudopods. Specific localization of ARL4C, IQGAP1, and MMP14 was the active site of invasion, which induced degradation of the extracellular matrix. Moreover, subcutaneously injected antisense oligonucleotide against ARL4C into tumor-bearing mice suppressed metastasis of pancreatic cancer. These results suggest that ARL4C-IQGAP1-MMP14 signaling is activated at invasive pseudopods of pancreatic cancer cells.

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MicroRNA-301a promotes pancreatic cancer invasion and metastasis through the JAK/STAT3 signaling pathway by targeting SOCS5

Carcinogenesis ◽

10.1093/carcin/bgz121 ◽

2019 ◽

Vol 41 (4) ◽

pp. 502-514 ◽

Cited By ~ 9

Author(s):

Hui Hu ◽

Qin Zhang ◽

Weiqun Chen ◽

Tangwei Wu ◽

Shuiyi Liu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Cancer Cell ◽

Cell Invasion ◽

Pancreatic Cancer Cell ◽

Cancer Invasion ◽

Janus Kinase ◽

Cancer Cell Invasion ◽

Invasion And Metastasis ◽

And Migration

AbstractPancreatic cancer is one of the most lethal digestive malignant tumors. We had previously found that microRNA-301a (miR-301a) is a oncogenic microRNA whose recognized conduce to nuclear factor-kappa B (NF-κB) activation in pancreatic cancer, yet the underlying mechanisms of miR-301a in promoting pancreatic cancer invasion and migration is obscure. In this work we found that high expression of miR-301a in human pancreatic cancer patients is related to poor survival. Overexpression of miR-301a enhances pancreatic cancer cell invasion, angiogenesis and migration, whereas inhibition of miR-301a suppresses pancreatic cancer cell invasion and reduces orthotopic pancreatic tumor growth and metastasis. Furthermore, suppressor of cytokine signaling 5 (SOCS5) is identified as a target gene of miR-301a. We found that miR-301a suppressed the expression of SOCS5 leads to janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) activation and is related to poor overall survival of pancreatic cancer patients. Taken together, our data show for the first time that the feedback loop between miR-301a and JAK/STAT3 pathway may play a significant role in pancreatic cancer invasion and metastasis. Targeting the loop may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for pancreatic cancer.

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