The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications

Gu, Yunru; Fang, Yuan; Wu, Xi; Xu, Tingting; Hu, Tong; Xu, Yangyue; Ma, Pei; Wang, Qiang; Shu, Yongqian

doi:10.1186/s40164-023-00420-3

Experimental Hematology & Oncology

Table 1 Molecular mechanism and biological functions of SUMO enzymes in diverse cancers

From: The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications

Cancer	SUMO enzyme(s)	Substrate	Biological mechanisms and functions	Refs
GBM	UBC9	CRMP2	Promote cancer cell proliferation	[16]
	SUMO1	PML	Promote tumor malignancy via stabilizing c-Myc and GSCs maintenance	[17]
	SUMO1	FUS	Inhibit tumorigenesis via alleviating cells mitophagy	[18]
	SAE1,UBC9,SENP1	NR	Promote cancer cells proliferation and migration and inhibit apoptosis	[15]
NSCLC	SUMO1	YTHDF2	Promote tumor progression via increasing its binding affinity with m⁶A -modified mRNAs	[19]
	SUMO1	METTL3	Promote tumor progression via decreasing its m⁶A methyltransferase activity	[7]
	TRIM28	IRF	Promote tumorigenesis via regulating tumor microenvironment	[20]
	UBC9,PIAS4	SIRT1	Promote tumor progression via facilitating EMT	[21]
	UBC9,PIAS4,SUMO1	SLUG	Promote tumor progression via enhancing HDAC1 recruitment and metastasis	[22]
	PIAS1	PML	Promote tumorigenesis via increasing proteasome-mediated degradation of PML	[23]
	SUMO1	VEGFR2	Inhibit tumor progression via suppressing angiogenesis, proliferation, and migration.	[24]
SCLC	SAE2	NR	Promote tumor progression only in high c-Myc expression group	[25]
BRCA	UBC9	NR	Inhibit tumor malignancy through being upregulated by FOXP3	[26]
	SUMO2/3	MYC	Promote cancer cell metastasis	[27]
	SENP3	AKT1	Promote macrophage polarization via AKT1 phosphorylation and activation	[30]
	SENP1	GATA1	Promote metastasis and invasion via facilitating CSN5-mediated ZEB1 degradation	[31]
	SENP1	MYC	Promote tumorigenesis via decreased ubiquitination and stabilization of c-MYC	[29]
	CBX4,SUMO1	HTERT	Promote metastasis through facilitating EMT and repressing E-cadherin expression	[32]
	PIAS1	SNON	Promote metastasis via increasing EMT	[33]
OSCC	SUMO1	SMAD4	promote tumor progression via TGFβ1-induced SUMO1 conjunction	[34]
	SUMO1	MDM2	Promote tumor aggressiveness through increasingmdm2 expression	[35]
	SUMO1	PTEN	Inhibit tumor progression via suppressing AKT/mTOR signaling pathway	[36]
	SUMO1	SP1	Inhibit tumor progression and promote radiosensitization through decreasing SP1 activity and promoting PTEN transcription in a BetA-dependent manner	[37]
	SENP3,SENP5	NR	Promote tumorigenesis via regulating differentiation of cancer cells	[38]
ESCC	SUMO2/3	MCM10	Promote cancer cell proliferation and metastasis	[40]
	SUMO2/3	HSP27	Promote proliferation and migration via PKM2 upregulation and E-cadherin downregulation	[41]
STAD	PIAS2	P38	Promote metastasis via forming a positive loop feedback with ROS accumulation	[42]
	PIAS1,PIAS4	NR	Decrease risk of mortality among patient receiving second-line docetaxel-based therapy	[43]
	SUMO2/3	NSUN2	Promote tumor progression via maintaining its stability and methyltransferase activity	[44]
	SENP2	NDRG2	Inhibit tumor progression via stabilizing NDRG2	[45]
	UBC9,SUMO1	IGF-1R	Promote proliferation and migration via increasing transcription activity of SNAI2	[46]
	SAE2	NR	Promote tumor aggressiveness	[47]
COAD	SENP1	p21,p27	Promote cell growth through downregulating CDK inhibitors and suppressing G1 arrest	[48]
	SUMO1	p53	Promote cancer cell metastasis	[49]
	PIAS1	IRF-1	Inhibit tumor progression via IRF-1 nuclear translocation and subsequent apoptosis	[50]
HCC	UBC9,SUMO1	PKM2	Promote tumor progression via PKM2 excretion and TME reprogramming	[51]
	RANBP2	FTO	Promote cancer malignancy via downregulating GNAO1 mRNA expression	[52]
	SENP2	HNRNPK	Promote tumorigenicity via disrupting interaction between HNRNPK and p53	[53]
	SUMO1	MANF	Inhibit tumor progression through inhibiting the NF-κBNF-κB/Snail signal pathway	[54]
	UBC9,SUMO1	METTL3	Promote tumor metastasis via facilitating Snail expression in an m6A-dependent manner	[55]
	SUMO1	NRF2	Promote tumor malignancy via promoting de novo serine synthesis	[56]
	CBX4	HIF1α	Promote angiogenesis via enhancing HIF-1α transcriptional activity and VEGF expression	[57]
	SENP1	HIF1α	Promote tumorigenesis through enhancing hypoxia-induced stemness	[58]
PDAC	PIAS4	VHL	Promote tumor progression via inhibiting VHL-mediated HIF1α degradation	[60]
	SUMO2,UBC9	RNF40	Promote tumor aggressiveness via resolving DNA double-strand breaks	[61]
BLCA	SENP1	NR	Promote tumor recurrence	[62]
	SENP2	TBL(R)1	Inhibit metastasis via suppressing β-catenin nulear translocation and MMP13 activation	[63]
	UBC9	HNRNPA1	Promote lymphangiogenesis and LN metastasis via facilitating SOX18 transcription	[64]
RCC	SUMO1	HAF	Promote tumor progression through inducing HIF-2 transactivation	[65]
	SUMO2	VHL	Promote angiogenesis via HIF-α degradation inhibition	[66]
PC	UBC9	STAT4	Promote PCA progression via enhancing immunosuppressive phenotype of TAMs	[67]
CCA	UBC9,SUMO2/3	HADA3	Promote tumorigenesis through HPV 16E6 stimulation	[68]
	UBC9,PIAS1	FOXM1B	Inhibit HPV carcinogenesis through disturbing cell cycle process	[70]
EOC	UBC9	NR	Promote cancer cell proliferation via facilitating PI3K/AKT signaling pathway	[71]
	SENP1	HIF1α	Promote tumor progression via weakening sensitivity to chemotherapy	[72]
	PIAS4	SP1	Promote metastasis via suppressing SIRT1 transcription and enhancing EMT	[72]

GBM: glioblastoma; NSCLC: non-small cell lung cancer; SCLC: small cell lung cancer; BRCA: breast carcinoma; OSCC: oral squamous cell carcinoma; ESCC: esophageal squamous cell carcinoma; STAD: stomach adenocarcinoma; COAD: colon adenocarcinoma; HCC: hepatocellular carcinoma; PDAC: pancreatic ductal adenocarcinoma; BLCA: bladder cancer; RCC: renal cell cancer; PC: prostate cancer; CCA: cervical cancer; EOC: epithelial ovarian cancer

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ISSN: 2162-3619

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