EGF promotes invasion by PANC-1 cells through Rac1/ROS-dependent secretion and activation of MMP-2

Syk Tyrosine Kinase Acts as a Pancreatic Adenocarcinoma Tumor Suppressor by Regulating Cellular Growth and Invasion

“…46 MMP2 mediates Panc1 invasion in response to epidermal growth factor, 47 suggesting that the MMP2 axis might be at least partly responsible for the high basal invasion we observed in Panc1/mock cells. RT-PCR verified the Affymetrix results of MMP2 and TIMP2 expression and further demonstrated a minimal effect of stable syk expression on the mRNA levels of the other gelatinase MMP9 and its cognate partner TIMP1 ( Figure 6C).…”

“…It is not currently known whether this deficiency represents a lack of growth factor stimulation or a lack of proteolytic enzyme source. However, because Panc1 cells express significant levels of MMP2 and invade in an EGF-dependent manner, 47 it is probably the former. A similar suppression of invasion was observed in Panc1 cells reexpressing syk due to 5AzaC treatment.…”

Rac1-mediated Mitochondrial H2O2 Generation Regulates MMP-9 Gene Expression in Macrophages via Inhibition of SP-1 and AP-1

“…In addition to other MAPKs, the ERK MAPK has been shown to modulate MMP expression (12). Inhibition of ROS by flavoenzyme inhibitors or antioxidants has been shown to decrease MMP expression (8,14,15).…”

“…Its role in mediating ROS generation has been implicated in many disease processes, including fibrosis (17)(18)20). Studies in which Rac1 has been shown to regulate MMP production via increased ROS were performed in non-phagocytic cells, such as fibroblasts, epithelial cells, and adenocarcinoma cells, and reduction of ROS decreased MMP expression and activity (14,15,21,22). However, the molecular mechanism(s) by which Rac1 modulates MMP-9 gene transcription, and the basis of these actions in phagocytic cells has not been demonstrated.…”

p38MAPK and ERK1/2 dictate cell death/survival response to different pro-oxidant stimuli via p53 and Nrf2 in neuroblastoma cells SH-SY5Y

“…Today, non-physiological alterations of the intracellular redox state are well established hallmarks of tumor biology, due to their implication in several transforming events, such as self-sufficiency in growth signals [2], apoptosis evading [3], sustained angiogenesis [4,5], autophagy [6,7] and tissue invasion [8,9]. This has been exploited by chemotherapeutic strategies based on the use of ROS-generating molecules (e.g., 2-metoxyestradiol and anthracyclins) to selectively kill transformed cells [10][11][12].…”