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. 2016 Jan 7;529(7584):97-100.
doi: 10.1038/nature16466. Epub 2015 Dec 23.

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

Elaine E Storm  1 , Steffen Durinck  2 , Felipe de Sousa e Melo  1 , Jarrod Tremayne  3 , Noelyn Kljavin  1 , Christine Tan  4 , Xiaofen Ye  5 , Cecilia Chiu  4 , Thinh Pham  6 , Jo-Anne Hongo  4 , Travis Bainbridge  7 , Ron Firestein  6 , Elizabeth Blackwood  3 , Ciara Metcalfe  3 , Eric W Stawiski  2 , Robert L Yauch  5 , Yan Wu  4 , Frederic J de Sauvage  1
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"V体育ios版" Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function

Elaine E Storm et al. Nature. .

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 VSports手机版. 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. .

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