SUMOylation regulates Rb hyperphosphorylation and inactivation in uveal melanoma

• Published in: Cancer science Vol. 113; no. 2; pp. 622 - 633
• Main Authors: Meng, Fengxi, Yuan, Yiqun, Ren, Hui, Yue, Han, Xu, Binbin, Qian, Jiang
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-02-2022; John Wiley and Sons Inc
• Subjects: Animals; Antibodies; Apoptosis; Cancer; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation; Cyclin-dependent kinases; Gene expression; ginkgolic acid; Humans; Kinases; Laboratories; Malignancy; Medical prognosis; Melanoma; Melanoma - metabolism; Melanoma - pathology; Metastasis; Mice; Mutation; Original; Patients; Phosphorylation; Plasmids; Proteins; Retina; Retinoblastoma; Retinoblastoma Binding Proteins - metabolism; Retinoblastoma protein; Software; SUMO protein; SUMO-1 Protein - metabolism; SUMOylation; Sumoylation - drug effects; Sumoylation - physiology; Telomerase; Tumors; Ubiquitin; Ubiquitin-Protein Ligases - metabolism; uveal melanoma; Uveal Neoplasms - metabolism; Uveal Neoplasms - pathology; Rb; SUMOylation; ginkgolic acid; phosphorylation; uveal melanoma
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15223

Small ubiquitin‐like modifier (SUMO)ylation is one of the posttranslational modifications and is implicated in many tumor types. Modulation of SUMOylation can affect tumor progression, but the underlying mechanisms remain unclear. Here, we show that, for the first time, in uveal melanoma (UM), the most common intraocular malignancy in adults, global SUMOylation is upregulated and participates in tumor growth. Inhibition of SUMOylation in UM is sufficient to reduce tumor growth both in vitro and in vivo. Furthermore, we found that retinoblastoma protein (Rb) is a target protein and a critical downstream effector of the upregulated SUMOylation activity in UM. Increased SUMOylation of the Rb protein leads to its hyperphosphorylation and inactivation in UM cells, promoting UM cell proliferation. In summary, our results provide novel insight into the mechanism underlying SUMOylation‐regulated tumor growth in UM.
Modulation of small ubiquitin‐like modifier (SUMO)ylation can affect tumor progression, but the underlying mechanisms remain largely enigmatic. Here, we report that SUMOylation is significantly upregulated in uveal melanoma (UM) and promotes tumor growth. Mechanically, we report that retinoblastoma protein is a target protein and the critical downstream effector of the upregulated SUMOylation in UM.