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. 2022 Sep 6;11(1):51. doi: 10.1038/s41389-022-00430-6

Fig. 5. UHRF1 decreases SEMA3E expression through suppression of AMPK activation to induce angiogenesis.

Fig. 5

A, B Western blot analysis of (A) SEMA3E in SJSA-1 and SaOS-2 VC and KO osteosarcoma cell lines quantification of KO normalized to VC; and (B) activated AMPK (pAMPK) and total AMPK with the quantification of the ratio. UHRF1 used to confirm VC and KO status. β-actin was used as a loading control. C Early phase sprouting angiogenesis (day 3) using human lung fibroblasts as assay control and SJSA-1 VC and KO cells with inducible sgRNA to knockout SEMA3E upon doxycycline addition in the fibrin gel bead assay. Quantified as the number of sprouts per bead. n = 30. ns not significant, *P < 0.05, ****P < 0.0001, by unpaired t test. D Model of UHRF1 oncogenic function in osteosarcoma. UHRF1 overexpression stimulates proliferation, exosome and uPA production that stimulates migration, invasion, and metastasis. UHRF1 also suppresses AMPK activation to inhibit SEMA3E and induce angiogenesis. Downstream of UHRF1, inhibitors of exosome secretion (e.g., GW4869), exosome endocytosis (CPZ), or uPA inhibitors (e.g., amiloride, BC11 hydrobromide) are attractive therapeutic options to decrease migration and metastasis. The development of UHRF1-targeted therapeutics might result in a beneficial decrease in both tumor growth and pulmonary metastases.