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Figure 9 | Molecular Cancer

Figure 9

From: MYC regulates the unfolded protein response and glucose and glutamine uptake in endocrine resistant breast cancer

Figure 9

UPR in glutamine-only conditions can lead to both pro-survival and pro-death outcomes. Effect of transfection of siRNA targeting GRP78, IRE1α, XBP1(s), and MYC for 24 h; or JNK inhibition with a small molecule inhibitor (SP600125) on growth in either glucose + glutamine or glutamine-alone media. Western blot (48 h); A-C, GRP78. D-F, IRE1α. G-I, JNK. J-L, XBP1. M-O, MYC. Inhibition of GRP78 did not significantly further affect cell numbers in glutamine-only conditions in both LCC1 and LCC9 cell lines, A. Western blot analysis of total GRP78 protein are shown in both cell lines in different conditions, B-C. Knockdown of IRE1α, D-F and XBP1, J-L, significantly increased inhibition of cell growth in glutamine-only conditions in both cell lines. However, inhibition of JNK with SP600125 significantly decreased the inhibition of cell growth in glutamine-only conditions, G-I. Also, knockdown of MYC, M-O, significantly decreased inhibition of cell growth in glutamine-only conditions. Overall, MYC may have facilitate an IRE1α-XBP1 pathway to promote cell survival during glutamine-only conditions, and an IRE1α-phospho-JNK pathway to promote cell death in this condition. ANOVA, p ≤ 0.001; *p < 0.05 for respective cell lines transfected with indicated siRNA (or treated with SP600125, for JNK) compared with control siRNA (or vehicle alone, for JNK) in glutamine-only conditions.

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