The JAK2/STAT3 signaling pathway is required for growth of CD44+CD24– stem cell–like breast cancer cells in human tumors
Lauren L.C. Marotta, … , David A. Frank, Kornelia Polyak
Lauren L.C. Marotta, … , David A. Frank, Kornelia Polyak
Published July 1, 2011; First published June 1, 2011
Citation Information: J Clin Invest. 2011;121(7):2723-2735. https://doi.org/10.1172/JCI44745.
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Research Article

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

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.

Authors

Lauren L.C. Marotta, Vanessa Almendro, Andriy Marusyk, Michail Shipitsin, Janina Schemme, Sarah R. Walker, Noga Bloushtain-Qimron, Jessica J. Kim, Sibgat A. Choudhury, Reo Maruyama, Zhenhua Wu, Mithat Gönen, Laura A. Mulvey, Marina O. Bessarabova, Sung Jin Huh, Serena J. Silver, So Young Kim, So Yeon Park, Hee Eun Lee, Karen S. Anderson, Andrea L. Richardson, Tatiana Nikolskaya, Yuri Nikolsky, X. Shirley Liu, David E. Root, William C. Hahn, David A. Frank, Kornelia Polyak

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Figure 3

Preferential activation of the IL-6/JAK2/Stat3 pathway in basal-like breast cancer cells.

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Preferential activation of the IL-6/JAK2/Stat3 pathway in basal-like bre...
(A) ELISA results. Error bars show SD of triplicates. (B) Immunoblots. Positive and negative controls were T-47D cells treated or not treated, respectively, with prolactin and oncostatin M. Stat3, pStat1, pStat5, and tubulin were used as controls. (C) Immunoblots. Two-hour treatment with 2 μM JAK inhibitor reduces pStat3 in basal-like breast cells containing it. pserStat3 and Stat3 were used as controls.