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, 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. AndersonAndrea L. Richardson, Tatiana Nikolskaya, Yuri Nikolsky, X. Shirley Liu, David E. Root, William C. Hahn, David A. Frank, Kornelia Polyak

Research output: Contribution to journalArticle

524 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2723-2735
Number of pages13
JournalJournal of Clinical Investigation
Volume121
Issue number7
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Marotta, L. L. C., Almendro, V., Marusyk, A., Shipitsin, M., Schemme, J., Walker, S. R., Bloushtain-Qimron, N., Kim, J. J., Choudhury, S. A., Maruyama, R., Wu, Z., Gönen, M., Mulvey, L. A., Bessarabova, M. O., Huh, S. J., Silver, S. J., Kim, S. Y., Park, S. Y., Lee, H. E., ... Polyak, K. (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), 2723-2735. https://doi.org/10.1172/JCI44745