Table 2.

Paradoxical role of ERAD components in tumor development.

ERAD components	Effects on tumor	Tumor types	Experimental approaches	Mechanisms of action	References
Derlin-1	Tumor promoting	Breast, bladder, colorectal cancer, and NSCLC	Knockdown studies by shRNA in human cell culture	A retrotranslocation channel protein upregulated in colorectal cancer cells	Tan et al. (2015), Dong et al. (2017), and Mao et al. (2018)
Derlin-3	Tumor promoting	Breast cancer	SiRNA inhibition in breast cancer cell lines	A retrotranslocation channel protein, whose inhibition results in decreased invasion and proliferation of cancer cells	Guiliano et al. (2014) and Shibata et al. (2017)
ERmanI	Tumor promoting	Breast cancer	Gene expression profiling of patient samples and gene inactivation by shRNA in human cancer cell lines	A mannosidase, its reduced expression inhibits N-glycosylation of substrates, impairing cancer cell survival	Legler et al. (2018)
HRD1	Tumor promoting	Colorectal cancer	Knockdown studies by shRNA in human cancer cell line	An E3, promoting degradation of misfolded proteins overexpressed in colorectal cancer	Tan et al. (2019)
P97	Tumor promoting	Colorectal, cervical cancer, and osteosarcoma	Small molecule and RNAi inhibition in human cancer cell lines	In complex with UFD1-NPL4 to facilitate substrate retrotranslocation in ERAD	Magnaghi et al. (2013)
NPL4	Tumor promoting	Breast cancer, myeloma, and osteosarcoma	Human cancer cell line and a murine model treated with disulfiram	In complex with P97 and UFD1 to facilitate substrate retrotranslocation in ERAD	Skrott et al. (2017)
UFD1	Tumor promoting	T-cell acute lymphoblastic leukemia	Gene inactivation studies in zebrafish models of leukemia and human leukemic cell lines.	In complex with P97 and NPL4 to facilitate substrate retrotranslocation in ERAD and its inactivation resulting in cytotoxic UPR responses	Huiting et al. (2018)
SEC22b	Tumor suppressing	Lymphoma and fibrosarcoma	Conditional mouse knockout specific in DCs	An ER-phagosome traffic mediator, facilitating cross-presentation in DCs	Alloatti et al. (2017)
CHIP	Tumor suppressing	Breast cancer	Gene inactivation by shRNA in mouse xenograft models and human cancer cell lines	An E3 facilitating degradation of misfolded substrates	Kajiro et al. (2009)
OS-9	Tumor suppressing	Pancreatic ductal adenocarcinoma	Measuring mRNA expression levels in patient samples of pancreatic ductal adenocarcinoma	A substrate recognition factor facilitating ERAD	Sun YW et al. (2014)
SEL1L	Tumor promoting or suppressing	Pancreatic and breast cancer	Overexpression and downregulation studies in murine models	A substrate recognition and recruitment factor, facilitating substrate retrotranslocation; overexpression of SEL1L results in reduced pancreatic cancer invasion, while its downregulation predicts poor prognosis of breast cancer	Orlandi et al. (2002), Cattaneo et al. (2005), and Jeon et al. (2015)
GP78	Tumor promoting or suppressing	HCC, colorectal, esophageal, bladder, and breast cancer	Correlation studies in patients, knockout studies in mice, and gene inactivation studies by shRNA in murine models	An E3 participating in substrate degradation; high GP78 expression predicts poor prognosis of patients with esophageal squamous cell carcinoma, colorectal, and bladder cancer; Gp78−/− knockout increases HCC development; Gene inactivation shows tumor suppressive effect of GP78 in breast cancer	Nakamori et al. (1994), Otto et al. (1994), Maruyama et al. (1995), Silletti and Raz (1996), Zhang, Kho, et al. (2015), and Chang et al. (2016)