Dataset Information

Neddylation of Insulin receptor substrate acts as a bona fide suppressor for cancer cell migration

ABSTRACT: Hyperinsulinemia, often associated with obesity and type 2 diabetes mellitus, is also linked to an elevated risk of various cancers. However, the specific mechanisms underlying this connection remain unclear. Here, we report that inhibiting neddylation, in the presence of insulin treatment, further promotes cancer cell migration in different cancer types by activating both insulin receptor substrate 1 and 2, as well as the PI3K/AKT signaling pathway. We also found that C-CBL neddylates IRS1 and IRS2 as an E3 ligase, with clinical evidence supporting its role as a tumor suppressor. Altogether, these findings suggest that the neddylation of IRS1 and IRS2 may be a bona fide suppressor of cancer cell migration. Thus, caution is advised when considering neddylation inhibitors as a treatment for cancer patients with obesity-related type 2 diabetes or hyperinsulinemic condition.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Ara Cho

LAB HEAD: Eugene C. Yi

PROVIDER: PXD044760 | Pride | 2024-05-22

REPOSITORIES: Pride

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Neddylation of insulin receptor substrate acts as a bona fide regulator of insulin signaling and its implications for cancer cell migration.

Park Jun Bum JB Moon Geon Ho GH Cho Ara A Kwon Minji M Park Jong-Wan JW Yi Eugene C EC Kim Haeryoung H Fukuda Junji J Kwak Cheol C Ko Young-Gyu YG Chun Yang-Sook YS

Cancer gene therapy 20240125 4

Irregularities in insulin signaling have significantly increased the risk of various cancers, yet the precise underlying mechanisms remain unclear. Within our study, we observed that inhibiting neddylation enhances cancer cell migration across different cancer types by activating both insulin receptor substrates 1 and 2 (IRS1 and IRS2), along with the PI3K/AKT signaling pathway. Notably, in the context of high-grade serous carcinoma (HGSC) patients, whether they had type 2 diabetes mellitus or n ...[more]

PMID: 38272982

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Dataset Information

Neddylation of Insulin receptor substrate acts as a bona fide suppressor for cancer cell migration

Publications

Neddylation of insulin receptor substrate acts as a bona fide regulator of insulin signaling and its implications for cancer cell migration.

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