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IGF1R deficiency decreases proliferation, DNA damage, senescence, and vascularization, attenuates tumor invasion by reduced EMT and fibrosis, and induces apoptosis upon pulmonary metastasis To determine the effect of IGF1R deficiency in the metastatic TME, we immunostained lung tumors of LLC-challenged mice for the following markers: Ki67 (proliferation), 53BP1 (DNA damage), p21 (senescence), C3 (apoptosis), CD31 and CD34 (vascularization), SOX9 (epithelial-mesenchymal transition, EMT), as well as Vimentin, Fibronectin, SMA and Masson (fibrosis)

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FOXO4-DRI may inhibit the FOXO4 translocation to the nucleus, potentially reducing oxidative stress defenses but primarily in senescent cells