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. Author manuscript; available in PMC: 2017 Mar 15.
Published in final edited form as: Nature. 2016 Aug 31;537(7620):422–426. doi: 10.1038/nature19347

Figure 3. PGC1α transcriptionally activates ID2 to suppress TCF4 activity and the pro-metastatic program.

Figure 3

a–c, ID2 knockdown in A375P cells increases integrin expression (a), migration/invasion (b) and metastasis (c, n=5 mice/group). d–f, Ectopic expression of ID2 attenuates PGC1α depletion-mediated activation of integrin, TGFβ and Wnt pathways (d) and induction of invasion (e) and metastasis (f, n=9 mice/group). g, TCF4 is required for the induction of integrins by ID2 inhibition. h, ID2 interacts with TCF4 in A375P cells. i–j, Ectopic expression of TCF4 increases integrin mRNAs (i) through directly binding to promoters of integrin genes (j) in A375P cells. k–l, TCF4 depletion represses invasion (k) and metastasis (l, n=8 mice/group) induced by PGC1α or ID2 knockdown in A375P cells. Images in b, c, e, f and k represent one picture captured with scale bar representing 200 microns; specifically, scale bars in b, A375P invasion, represent 100 microns. Values in a, d, g, i, j and k represent mean ± SD of independent biological triplicates representative of three experiments; values in c, f and l represent mean ± SEM of indicated amount of mice; in a, c, d, f, g, i, j, k and l, *p < 0.05, **p < 0.01 and ***p < 0.005 by Student’s t-test.