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The JAK2/STAT3 signaling pathway is required for growth of CD44⁺CD24⁻ stem cell-like breast cancer cells in human tumors

Marotta, Lauren L.C and Almendro, Vanessa and Shipitsin, Michail and Marusyk, Andriy and Schemme, Janina and Walker, Sarah R and Bloushtain-Qimron, Noga and Kim, Jessica J and Choudhury, Sibgat A and Maruyama, Reo and Wu, Zhenhua and Gönen, Mithat and Mulvey, Laura A and Bessarabova, Marina O and Huh, Sung Jin and Silver, Serena J and Kim, So Young and Park, So Yeon and Lee, Hee Eun and Anderson, Karen S and Richardson, Andrea L and Nikolskaya, Tatiana and Nikolsky, Yuri and Liu, X Shirley and Root, David E and Hahn, William C and Frank, David A and Polyak, Kornelia and Ritson, Margaret (2011) The JAK2/STAT3 signaling pathway is required for growth of CD44⁺CD24⁻ stem cell-like breast cancer cells in human tumors. Journal of Clinical Investigation, 121 (7). pp. 2723-2735. ISSN 0021-9738

Official URL: http://www.jci.org/121/7

Abstract

Intratumor heterogeneity is a major clinical problem because tumor cell subtypes display variable sensitivity to therapeutics and may play different roles in progression. We previously characterized 2 cell populations in human breast tumors with distinct properties: CD44+CD24- cells that have stem cell-like characteristics, and CD44-CD24+ cells that resemble more differentiated breast cancer cells. Here we identified 15 genes required for cell growth or proliferation in CD44+CD24- human breast cancer cells in a large-scale loss-of-function screen and found that inhibition of several of these (IL6, PTGIS, HAS1, CXCL3, and PFKFB3) reduced Stat3 activation. We found that the IL-6/JAK2/Stat3 pathway was preferentially active in CD44+CD24- breast cancer cells compared with other tumor cell types, and inhibition of JAK2 decreased their number and blocked growth of xenografts. Our results highlight the differences between distinct breast cancer cell types and identify targets such as JAK2 and Stat3 that may lead to more specific and effective breast cancer therapies.

Item Type: Article
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/2737

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