Table 1.

The roles of DUBs in cancers.

DUB	Roles	Target	Function	Consequences
USP1	Promotor	ULK1, EZH2, ID1/2/3, CHK1	Stabilization	Promote proliferation, metastasis, cancer cell stemness, and regulate DDR[ 117 , 118 , 282 , 283 ]
USP2	Promotor	CCND1, CCNA1, FAS, MDM2, MDM4, TβRI	Stabilization	Promote proliferation and metastasis, evade apoptosis[ 284 , 285 , 286 , 287 , 288 ]
USP3	Promotor	SUZ12	Stabilization	Boost metastasis[ 289 ]
	Suppressor	p53	Stabilization	Inhibit proliferation[ 290 ]
USP4	Promotor	HDAC2, ARF‐BP1, TβRI, Twist1, β‐catenin, PRL‐3, CYPA,	Stabilization	Promote proliferation and metastasis, decrease sensitivity to chemotherapy[ 91 , 144 , 147 , 291 , 292 , 293 ]
USP5	Promotor	c‐Maf, Slug, β‐catenin	Stabilization	Evade apoptosis, promote metastasis[ 294 , 295 , 296 ]
USP6	Promotor	c‐Jun, Fzd, JAK1	Stabilization	Promote metastasis and tumor growth[ 297 , 298 , 299 ]
USP7	Promotor	CDC25A, N‐Myc, Ki‐67, HIF‐1α, MDM2, MDM4, PHF8, MDC1, β‐catenin, LSD1, NOTCH1, HDM2	Stabilization	Antagonize p53‐involved tumor suppression regulations, Promoting tumor metastasis, decrease drug sensitivity, regulate DDR[ 135 , 300 , 301 , 302 , 303 , 304 , 305 , 306 , 307 , 308 , 309 , 310 , 311 , 312 , 313 , 314 , 315 , 316 , 317 ]
	Suppressor	PD‐L1	Stabilization	Anti‐tumor immune response[ 257 ]
USP8	Promotor	Cx43, AKT, TβRII, PD‐L1	Stabilization	Promote proliferation and metastasis, inhibit immonotherapy[ 318 , 319 ]
USP9X	Promotor	pVHL, CEP131, TRB3, SMAD4, SMURF1, TDRD3, β‐catenin	Stabilization	Promoting proliferation and metastasis, evade apoptosis[ 320 , 321 , 322 , 323 , 324 , 325 , 326 , 327 , 328 , 329 , 330 ]
	Suppressor	YAP1, TIK, MCL1, XIAP, Ets‐1, IRS‐2, CLASPIN, FBW7, AMOT, ITCH, LATS2, CLASPIN	Stabilization or altered activity	Maintain DNA replication fork stability and inhibit proliferation[ 127 , 321 , 324 , 331 , 332 ]
USP10	Promotor	SMAD4, Slug, TOP2α, FLT3, G3BP2	Stabilization or altered activity	Promote tumorigenesis and metastasis[ 333 , 334 , 335 , 336 ]
	Suppressor	MSH2, p53, SIRT6, p14ARF, AMPKα, PTEN, MSH2	Stabilization	Suppress tumor progression and increase apoptosis, regulate cellular sensitivity to DNA damage[ 88 , 337 , 338 , 339 ]
USP11	Promotor	XIAP, cIAP2, RAE1, PPP1CA, NF90, eIF4B, TβRII	Stabilization	Promote proliferation and metastasis, evade apoptosis[ 340 , 341 , 342 , 343 , 344 , 345 , 346 , 347 ]
	Suppressor	VGLL4, ARID1A, PTEN, Mgl‐1, p21, PML, BRCA2	Stabilization or altered activity	Inhibit tumorigenesis and metastasis, regulate DDR[ 123 , 124 , 348 , 349 , 350 , 351 , 352 , 353 , 354 ]
USP12	Promotor	AR, MDK, MDM2	Stabilization	Maintain malignant traits and promote angiogenesis[ 355 , 356 , 357 ]
USP13	Promotor	MCL1, c‐Myc, MITF RAP80, ACLY, OGDH	Stabilization	Promote proliferation and metabolism, chemotherapy resistance[ 358 , 359 , 360 , 361 , 362 ]
	Suppressor	PTEN, RAP80‐BRCA1	Stabilization	Anti‐tumor and regulate DDR[ 359 , 363 ]
USP14	Promotor	PI3K, Dvl, Vimentin, Aurora B, AR	Stabilization	Promote proliferation and metastasis, prevent apoptosis and regulate DDR[ 103 , 105 , 364 , 365 , 366 , 367 ]
USP15	Promotor	TOP2α, MDM2, TβRI, HBx	Stabilization or altered activity	Promote metastasis and inhibit anti‐tumor immunoresponses[ 368 , 369 , 370 , 371 ]
	Suppressor	Keap1, IRS2, p53	Stabilization or altered activity	Inhibit tumorigenesis and decrease chemo‐resistance[ 372 , 373 , 374 ]
USP17	Promotor	CDC25A, Geminin, HAS2, Slug, Snail, Twist, SMAD4, BRD4	Stabilization	Promote tumorigenesis and metastasis, prevent apoptosis[ 166 , 311 , 375 , 376 , 377 , 378 , 379 ]
USP18	Promotor	ZEB1, RARα, BCL2L1, KRAS	Stabilization	Promote tumorigenesis and metastasis, prevent apoptosis[ 380 , 381 , 382 , 383 ]
USP19	Suppressor	HDAC1/2	Altered activity	Maintain genomic stability[ 384 ]
USP20	Promotor	β‐catenin	Stabilization	Promote tumorigenesis[ 385 ]
	Suppressor	TRAF6, Tax, CLASPIN	Stabilization or altered activity	Inhibit tumorigenesis[ 386 , 387 ]
USP21	Promotor	EZH2, BRCA2, MEK2, PD‐L1	Stabilization	Promote tumorigenesis, metastasis, immune escape[ 265 , 388 , 389 , 390 , 391 ]
	Suppressor	Fra‐1, MARK1	Stabilization	Anti‐tumor[ 392 ]
USP22	Promotor	CCNB1, CCND1, c‐Myc, FBP1, BMI1, COX‐2, EGFR, H2A, KDM1A, SIRT1, PD‐L1	Altered activity or stabilization	Promote proliferation, metastasis and cancer stemness, drug resistance, reduce sensitivity to immune therapy, regulateγH2AX‐mediated DDR[ 265 , 359 , 393 , 394 , 395 , 396 , 397 , 398 , 399 , 400 , 401 ]
	Suppressor	PU.1	Stabilization	Anti‐differentiation[ 402 ]
USP24	Promotor	β‐TrCP, MCL‐1	Stabilization	Promote cancer malignancy[ 403 , 404 ]
	Suppressor	Bax, E2F4, p300, Securin	Stabilization	Promote apoptosis[ 405 ]
USP26	Promotor	AR, Snail	Altered activity or Stabilization	Promote proliferation and metastasis[ 406 , 407 ]
	Suppressor	SMAD7	Stabilization	Inhibit metastasis[ 406 ]
USP27	Promotor	Cyclin E	Stabilization	Pro‐tumor effects[ 408 ]
USP28	Promotor	c‐Myc, Fbw7	Stabilization	Promote tumorigenesis and metastasis[ 409 , 410 , 411 , 412 , 413 ]
	Suppressor	LIN28A, LSD1, c‐Jun, NICD1, p53	Stabilization	Arrest cell cycle[ 414 ]
USP29	Promotor	Claspin, Snail	Stabilization	Promote tumorigenesis and metastasis[ 415 , 416 ]
	Suppressor	p53	Stabilization	Inhibit proliferation[ 417 ]
USP30	Promotor	TOM20, DRP1	Stabilization	Promote migration, evade apoptosis[ 418 , 419 ]
USP33	Promotor	SP1	Stabilization	Pro‐tumor effects[ 420 , 421 ]
	Suppressor	PPM1A, Robo1, β‐arrestin2	Altered activity or Stabilization	Inhibiting tumor metastasis[ 422 , 423 , 424 ]
USP35	Suppressor	ABIN‐2	Stabilization	Inhibit proliferation[ 425 ]
USP36	Promotor	c‐Myc, DHX33, CHD7, H2B	Altered activity or stabilization	Promote tumorigenesis and proliferation[ 426 , 427 , 428 , 429 ]
USP37	Promotor	RARA, Gli1, Snail, 14‐3‐3γ, c‐Myc	Stabilization	Promote proliferation and metastasis[ 430 , 431 , 432 , 433 , 434 ]
	Suppressor	p27	Stabilization	Inhibit proliferation[ 435 ]
USP42	Suppressor	p53	Stabilization	Inhibit proliferation[ 436 ]
USP43	Promotor	H2B, ZEB1	Altered activity or Stabilization	Promote proliferation and metastasis[ 156 , 437 ]
USP44	Promotor	H2B, EZH2, Securin	Altered activity or Stabilization	Promote proliferation and metastasis[ 438 , 439 , 440 , 441 ]
USP46	Promotor	CDT2, ENO1	Stabilization	Promote proliferation and metastasis[ 442 , 443 ]
	Suppressor	PHLPP	Stabilization	Inhibit proliferation[ 444 ]
USP47	Promotor	β‐catenin, Snail	Stabilization	Promote proliferation and metastasis[ 445 , 446 , 447 ]
USP48	Promotor	TRAF2, Gli1	Stabilization	Promote tumorigenesis and metastasis[ 448 ]
USP49	Suppressor	p53, FKBP51	Stabilization	Inhibit proliferation and regulate DDR[ 449 , 450 ]
USP51	Promotor	ZEB1, FAT4	Stabilization	Promote proliferation and metastasis[ 451 , 452 ]
USP52	Promotor	ASF1A	Stabilization	Drug resistance[ 453 ]
CYLD	Suppressor	Dvl, p53, TRAF2, Bcl‐3, c‐Jun, c‐Fox	Stabilization	Suppress tumorigenesis and metastasis, promote apoptosis, regulate DDR[ 454 , 455 , 456 , 457 , 458 , 459 , 460 ]
OTUB1	Promotor	c‐IAP1, FOXM1, Snail, SLC7A11, PD‐L1, UBC13	Stabilization	Promote tumorigenesis, metastasis and immune escape, regulate DDR[ 131 , 461 , 462 , 463 , 464 , 465 ]
	Suppressor	Erα, RPA1, DEPTOR	Stabilization or altered activity	Suppress tumorigenesis[ 466 , 467 , 468 ]
OTUB2	Promotor	YAP/TAZ, U2AF2	Stabilization	Promote metastasis[ 68 , 469 ]
OTUD1	Suppressor	YAP, p53, SMAD7	Stabilization or altered activity	Suppress tumorigenesis cancer stemness and metastasis[ 470 , 471 , 472 ]
OTUD2	Promotor	ITCH	Stabilization	Promote proliferation[ 473 ]
OTUD3	Promotor	GRP78	Stabilization	Promote tumorigenesis[ 474 ]
	Suppressor	PTEN, p53	Stabilization	Inhibit proliferation and induce apoptosis[ 475 , 476 ]
OTUD5	Suppressor	p53, PDCD5, UBR5	Stabilization	Promote apoptosis and drug sensitivity[ 477 , 478 , 479 ]
OTUD6B	Suppressor	pVHL	Stabilization	Inhibit metastasis[ 480 ]
OTUD7A	Suppressor	TRAF6	Altered activity	Inhibit metastasis[ 481 ]
OTUD7B	Promotor	GβL, Aurora A, Cyclin B, EGFR	Stabilization or altered activity	Promote turiogenesis, proliferation, angiogenesis[ 482 , 483 , 484 , 485 ]
A20	Promotor	ERα	Stabilization	Promote proliferation[ 486 ]
TRABID	Promotor	EZH2	Stabilization	Promote proliferation[ 487 ]
	Suppressor	Twist1	Altered activity	Inhibit metastasis[ 488 ]
UCHL1	Promotor	HIF‐1α, TβRI, SMAD2	Stabilization	Pro‐metastasis[ 169 , 489 ]
	Suppressor	NOXA, p53	Stabilization	Inhibit proliferation, induce chemosensitivity[ 141 , 490 ]
UCHL3	Promotor	TDP1	Stabilization	Drug resistance[ 491 ]
UCHL5	Promotor	TβRI, PRP19	Stabilization	Promote tumorigenesis and metastasis[ 107 , 492 ]
BAP1	Suppressor	H2A, γ‐tubulin, Ino80, IP3R3, MCRS1	Altered activity or Stabilization	Maintain chromosomal stability, inducecell apoptosis[ 493 , 494 , 495 , 496 , 497 ]
ATXN3	Promotor	KLF4	Stabilization	Promote proliferation[ 498 ]
	Suppressor	p53	Stabilization	Induce apoptosis[ 499 ]
ATXN3L	Promotor	KLF5	Stabilization	Promote proliferation[ 500 ]
POH1	Promotor	E2F1	Stabilization	Promote proliferation[ 98 ]
COPS5	Promotor	PD‐L1, HK2, Trx, Snail, Survivin, FOXM1, ZEB1	Stabilization	Reduce sensitivity to immune therapy, promote proliferation and metastasis[ 263 , 501 , 502 , 503 , 504 , 505 ]
COPS6	Promotor	CHIP, CTSL, PD‐L1	Altered activity	Promote immune escape, promote proliferation and metastasis[ 506 , 507 , 508 ]
AMSH	Promotor	Slug	Stabilization	Promote metastasis[ 509 ]
BRCC36	Promotor	NuMA	Altered activity	Pro‐proliferation[ 510 ]
MYSM1	Suppressor	H2A	Altered activity	Anti‐tumor effects[ 511 ]