Skip to main content
. Author manuscript; available in PMC: 2022 Dec 27.
Published in final edited form as: Cell Rep. 2022 Dec 6;41(10):111759. doi: 10.1016/j.celrep.2022.111759

Figure 4. MYC-mediated IRS2 regulation of breast cancer stemness.

Figure 4.

(A) ALDH activity of IRS1−/−, IRS2−/− SUM-159 cells expressing EV or IRS2 after treatment with the Myc inhibitor 10074-G5. The ALDH inhibitor DEAB was included as a negative control.

(B) IRS1−/−, IRS2−/− SUM-159 cells expressing EV or IRS2 were assayed for mammospheres in the absence or presence of 10074-G5 in B27+ supplement.

(C) Irs2−/− PyMT cells expressing EV, Myc-WT, and Myc-T58A were analyzed for mammospheres in B27+ supplement.

(D) In vitro limiting-dilution assay of Irs2−/− PyMT cells expressing EV, Myc-WT, and Myc-T58A.

(E) Model for IRS2/PI3K-dependent regulation of breast cancer stemness. IRS2/PI3K mediates IIS-induced inactivation of GSK3β through phosphorylation on serine 9. Inactive pS9-GSK3β lacks the ability to phosphorylate threonine 58 of MYC, thus blocking proteasome-mediated degradation of MYC and allowing active pS62-MYC to accumulate. Created with BioRender.com.

The mammosphere data shown in all graphs represent the mean ± SD of a representative experiment performed three times independently. The ALDH data shown represent the mean ± SD of three independent experiments. *p < 0.05; **p < 0.01; ***p < 0.001.

See also Figure S4.