Dataset Information

A basigin antibody modulates MCTs to impact tumor metabolism and immunity

ABSTRACT: Lactate metabolism and signaling intricately intertwine in the context of cancer and immunity. Basigin, working alongside monocarboxylate transporters MCT1 and MCT4, orchestrates the movement of lactate across cell membranes. Despite promising potential in treating aggressive tumors, the impact of basigin antibodies on these interactions remains unclear. Our research sheds light on this complex interplay: basigin positively modulates MCT activity. A basigin antibody transforms basigin into a negative regulator of MCTs. The antibody suppresses lactate transport and enhances anti-tumor immunity in vitro and in vivo. Furthermore, antibody alters metabolic profiles in PDOs-NSCLCs and T cells. Cryo-EM structure analysis and molecular dynamics simulations unveil that MCT1’s turnover rate is influenced by the flexibility of basigin’s Ig2 domain. By restricting Ig2 flexibility, antibody reduces MCT1 turnover. These findings underscore the promise of basigin antibodies in tumor combat by influencing metabolism and immunity and the value of shared ancillary subunits in targeting heteromeric transporters.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268751 | GEO | 2025/05/14

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Many cancers rely on glycolytic metabolism to fuel rapid proliferation. This has spurred interest in designing drugs that target tumor glycolysis such as AZD3965, a small molecule inhibitor of Monocarboxylate Transporter 1 (MCT1) currently undergoing Phase I evaluation for cancer treatment. Since MCT1 mediates proton-linked transport of monocarboxylates such as lactate and pyruvate across the plasma membrane (Halestrap and Meredith, 2004), AZD3965 is thought to block tumor growth through disruption of lactate transport and glycolysis. Here we show that MCT1 inhibition impairs proliferation of glycolytic breast cancer cells that express MCT4 via disruption of pyruvate rather than lactate export. We found that MCT1 expression is elevated in glycolytic breast tumors and cell lines as well as in malignant breast and lung tissues. High MCT1 expression predicts poor prognosis in breast and lung cancer patients. Stable knockdown and AZD3965-mediated inhibition of MCT1 promote oxidative metabolism. Acute inhibition of MCT1 reduces pyruvate export rate but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that also express MCT4. Despite the lack of glycolysis impairment, MCT1 loss-of-function decreases breast cancer cell proliferation and blocks growth of mammary fat pad xenograft tumors. Our data suggest that MCT1 expression is elevated in glycolytic cancers to promote pyruvate export, which when inhibited enhances oxidative metabolism and reduces proliferation. This study presents an alternative molecular consequence of MCT1 inhibitors that further supports their use as anti-cancer therapeutics. Since MCT1 levels are elevated in glycolytic and malignant breast tumors, we hypothesized that MCT1 may contribute to the Warburg effect metabolic phenotype. To test this hypothesis, we generated whole genome microarray data from breast cancer cell lines either a) expressing a short hairpin (sh)RNA-mediated stable knockdown of MCT1; or b) treated for 24 hours with an MCT1 inhibitor (AZD3965). Scramble shRNA or DMSO were used as controls, and all conditions were analzed in triplicate. The cell lines used â HS578T, SUM149PT, and SUM159PT â are among the most glycolytic in a panel of 31 breast cancer cell lines.

Dataset Information

A basigin antibody modulates MCTs to impact tumor metabolism and immunity

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets