The JAK2/STAT3 signaling pathway is required for growth of CD44 +CD24- stem cell-like breast cancer cells in human tumors Journal Article
| Authors: | 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.; Gonen, M.; Mulvey, L. A.; Bessarabova, M. O.; Huh, S. J.; Silver, S. J.; Kim, S. Y.; Park, S. Y.; Lee, H. E.; Anderson, K. S.; Richardson, A. L.; Nikolskaya, T.; Nikolsky, Y.; Liu, X. S.; Root, D. E.; Hahn, W. C.; Frank, D. A.; Polyak, K. |
| Article Title: | 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. |
| Keywords: | human cell; janus kinase 2; nonhuman; cell proliferation; mouse; gene; stat3 protein; breast cancer; cell growth; animal experiment; animal model; cell differentiation; tumor xenograft; cell population; stem cell; nucleotide sequence; cancer cell; interleukin 6; loss of function mutation; short hairpin rna; cxcl3 chemokine; cd44+ cd24- cancer cell; cd44- cd24+ cancer cell; has1 gene; pfkfb3 gene; ptgis gene |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 121 |
| Issue: | 7 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2011-07-01 |
| Start Page: | 2723 |
| End Page: | 2735 |
| Language: | English |
| DOI: | 10.1172/jci44745 |
| PROVIDER: | scopus |
| PMCID: | PMC3223826 |
| PUBMED: | 21633165 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 17 August 2011" - "CODEN: JCINA" - "Source: Scopus" |
