Asset Details
Do you wish to reserve the book?
Inhibition of autocrine HGF maturation overcomes cetuximab resistance in colorectal cancer
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Inhibition of autocrine HGF maturation overcomes cetuximab resistance in colorectal cancer
Do you wish to request the book?
Inhibition of autocrine HGF maturation overcomes cetuximab resistance in colorectal cancer
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Inhibition of autocrine HGF maturation overcomes cetuximab resistance in colorectal cancer
2024
Overview
Although amplifications and mutations in receptor tyrosine kinases (RTKs) act as bona fide oncogenes, in most cancers, RTKs maintain moderate expression and remain wild-type. Consequently, cognate ligands control many facets of tumorigenesis, including resistance to anti-RTK therapies. Herein, we show that the ligands for the RTKs MET and RON, HGF and HGFL, respectively, are synthesized as inactive precursors that are activated by cellular proteases. Our newly generated HGF/HGFL protease inhibitors could overcome both de novo and acquired cetuximab resistance in colorectal cancer (CRC). Conversely, HGF overexpression was necessary and sufficient to induce cetuximab resistance and loss of polarity. Moreover, HGF-induced cetuximab resistance could be overcome by the downstream MET inhibitor, crizotinib, and upstream protease inhibitors. Additionally, HAI-1, an endogenous inhibitor of HGF proteases, (i) was downregulated in CRC, (ii) exhibited increased genomic methylation that correlated with poor prognosis, (iii) HAI-1 expression correlated with cetuximab response in a panel of cancer cell lines, and (iv) exogenous addition of recombinant HAI-1 overcame cetuximab resistance in CC-HGF cells. Thus, we describe a targetable, autocrine HAI-1/Protease/HGF/MET axis in cetuximab resistance in CRC.
Publisher
Springer International Publishing,Springer Nature B.V
Subject
/ Biomedical and Life Sciences
/ Cancer
/ Colorectal Neoplasms - drug therapy
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - metabolism
/ Drug Resistance, Neoplasm - genetics
/ Hepatocyte Growth Factor - genetics
/ Hepatocyte Growth Factor - metabolism
/ Hepatocyte Growth Factor - pharmacology
/ Humans
/ Kinases
/ Ligands
/ Peptide Hydrolases - metabolism
/ Protease
/ Protease Inhibitors - pharmacology
/ Proto-Oncogene Proteins c-met - genetics
/ Proto-Oncogene Proteins c-met - metabolism
/ Tyrosine
