'Novel molecular targets for breast and lung cancer stem cells' Noriko Gotoh

Speaker: Prof. Noriko Gotoh

Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University

Title: Novel molecular targets for breast and lung cancer stem cells

Abstract: Cancer stem cells (CSCs) are thought to be responsible for the initiation and recurrence of tumors. Therefore, targeting molecules that have a critical role in maintenance of CSCs would be a useful strategy. Since the ErbB2/3-PI3K-NFkB pathway is important for cancer stemness, we examined expression of downstream molecules in this pathway by comprehensive analysis of gene expression profiles over time after addition of the ErbB3 ligand heregulin (HRG). Insulin-like growth factor 2 (IGF2) was identified as a key downstream molecule, since anti-IGF2 antibody treatment blocked tumor sphere formation of breast cancer cells, a characteristic of stemness, even under conditions where other growth factors/cytokines were present. IGF2-PI3K signaling induced tumor sphere formation and enhanced the expression of genes favoring stemness, including the transcription regulator ID1 and IGF2 itself. Consistent with these data, ID1 and the IGF2 receptor IGF-1R were expressed at high levels in cancer stem cell populations of breast cancer patient-derived xenografts (PDXs).

CD74-NRG1 fusion gene was identified in 5-15% of invasive mucinous adenocarcinoma of the lung. We expressed cDNA of CD74-NRG1 fusion gene in human cancer cells, and investigated whether this fusion gene is involved in the promotion of CSC phenotype. We examined the self-renewal ability by performing the sphere forming assay. CD74-NRG1 expressing lung and breast cancer cells were able to form tumor spheres, while cells infected with the lentivirus carrying control vector weren’t. We also analyzed the population of breast CSCs (BCSCs) by flow cytometry. The percentages of CD44^high/CD24^-/low BCSC-enriched population increased in CD74-NRG1 expressing cells. These results suggest that expression of CD74-NRG1 fusion gene promotes cancer stem cell properties and is involved in stem cell function of several types of cancers including lung and breast cancer.

References

1. Minegishi Y, Gotoh N, et al; Cancer Sci., 104, 345-352, 2013.
2. Hinorara K, Gotoh N, et al; Proc Natl Acad Sci, USA 109, 6584-6589, 2012.

Yamauchi M, Gotoh N, et al; PLoS ONE, 7, e43923, 2012.

Host: 

Open Technology Center

Cell Signal Unit