Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function

Elaine E. Storm, Steffen Durinck, Felipe de Sousa e Melo, Jarrod Tremayne, Noelyn Kljavin, Christine Tan, Xiaofen Ye, Cecilia Chiu, Thinh Pham, Jo-Anne Hongo, Travis Bainbridge, Ron Firestein, Elizabeth Blackwood, Ciara Metcalfe, Eric W. Stawiski, Robert L. Yauch, Yan Wu, Frederic J. de Sauvage

Research output: Contribution to journalArticleResearchpeer-review

111 Citations (Scopus)

Abstract

Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the stem-cell compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a stem-cell compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of stem-cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.

Original languageEnglish
Pages (from-to)97-100
Number of pages4
JournalNature
Volume529
Issue number7584
DOIs
Publication statusPublished - 7 Jan 2016
Externally publishedYes

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