Abstract:
:We have previously shown that N-cadherin expression is associated with tumor invasion, and that some cancer cells respond to specific extracellular matrix molecules by up-regulating N-cadherin. Pancreatic cancer is characterized by excessive deposition of type I collagen. Here, we show that human pancreatic cancer cells respond to collagen I, but not other matrices, by increasing motility and up-regulating mesenchymal markers, including N-cadherin. Both collagen I-mediated motility and metastasis in a mouse model for pancreatic cancer were inhibited by N-cadherin knockdown. Furthermore, inhibiting c-Jun NH(2)-terminal kinase (JNK) with chemical inhibitors or short hairpin RNA abrogated all collagen I-induced changes. We show that JNK1 is activated in response to collagen I, which increases tumorigenesis by up-regulating N-cadherin expression and by increasing motility.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Shintani Y,Hollingsworth MA,Wheelock MJ,Johnson KRdoi
10.1158/0008-5472.CAN-06-2322subject
Has Abstractpub_date
2006-12-15 00:00:00pages
11745-53issue
24eissn
0008-5472issn
1538-7445pii
66/24/11745journal_volume
66pub_type
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