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Nerve Growth Factor in Cancer Cell Death and Survival
Molloy, Niamh H.; Read, Danielle E.; Gorman, Adrienne M.
One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75NTR, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75NTR. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75NTR. This latter signaling through p75NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer.
Keyword(s): Apoptosis; Breast cancer; Nerve growth factor; p75 neurotrophin receptor; Prostate cancer; TrkA; School of Natural Science
Publication Date:
2011
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Contributor(s): Breast Cancer Campaign
Institution: NUI Galway
Publisher(s): MDPI
File Format(s): application/pdf
First Indexed: 2015-11-10 09:22:02 Last Updated: 2016-12-21 09:20:55