Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/16091
Title: Up-regulation of stem cell markers by P21-activated kinase 1 contributes to 5-fluorouracil resistance of colorectal cancer
Authors: Huynh, NHi;Shulkes, Arthur;Baldwin, Graham;He, Hong
Issue Date: 3-Jun-2016
EDate: 2016-06-03
Citation: Cancer Biology & Therapy 2016; online first: 3 June
Abstract: Cancer stem cells (CSC) are tumorigenic and resistant to chemotherapy. In colorectal cancer (CRC), CSCs have been identified by the expression of specific markers, including CD44, Bmi1 and Nanog. Although p21-activated kinase 1 (PAK1), acting downstream of Ras, stimulates Wnt/β-catenin signaling and is known to play an important role in CRC development and progression, the role of PAK1 in the expression of CSC markers has not previously been investigated. The effect of PAK1 over-expression, knockdown or inhibition on the expression or alteration (in the case of CD44) of CSC markers in human CRC cell lines was measured by immunofluorescence and Western blotting. The effect of PAK1 modulation on tumorigenesis, and on resistance to treatment with 5-fluorouracil (5-FU), was measured by sphere formation in vitro and by growth of xenografted tumors in vivo. The results show that PAK1 activity correlated with the expression of CSC markers and the CD44 isoform profile, and with tumor growth both in vitro and in vivo. Furthermore PAK overexpression partially overcame the inhibition of CRC growth by 5-FU, and PAK inhibition was synergistic with 5-FU treatment. Our findings lay the foundation for a combination therapy in which PAK1 inhibitors targeting CSCs may be combined with conventional 5-FU-based chemotherapy for the treatment of CRC.
URI: http://ahro.austin.org.au/austinjspui/handle/1/16091
DOI: 10.1080/15384047.2016.1195045
PubMed URL: http://www.ncbi.nlm.nih.gov/pubmed/27260988
Type: Journal Article
Subjects: 5-FU
Cancer stem cell markers
PAK1
Colorectal cancer
Appears in Collections:Journal articles

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