Monocarboxylate transporter 1 is up‐regulated in basal‐like breast carcinoma

Abstract

These results provide evidence for a prognostic value of MCT1 in breast carcinoma and support the exploitation of the complex MCT1/CD147 as a promising target for cancer therapy, especially in basal-like breast carcinoma.

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

“…In this work, we analysed MCT1 and MCT4 expression, as well as the expression of other relevant proteins in cancer metabolism, in a variety of human breast cancer cell lines. MCT1 was strongly expressed at plasma membrane in MDA-MB-468, Hs578T and BT20 (basal-like subtype cells), in accordance with our findings for human breast carcinoma samples (Pinheiro et al 2010). In MDA-MB-231, also basal-like subtype cells, MCT1 was not detected, as described by others (Asada et al 2003, Gallagher et al 2007, Hussien & Brooks 2011, and the same was observed for the Her2-positive subtype cell line (SkBr3).…”

“…Recently, our group described an increase in MCT1 expression in breast carcinomas, when compared with normal tissue. This enhanced MCT1 expression, as well as the expression of CD147, a MCT1/MCT4 chaperone (Kirk et al 2000, Gallagher et al 2007, was associated with basal-like-subtype tumours and other poor prognostic parameters (Pinheiro et al 2010). Additionally, we found that MCT1, but not MCT4, was associated with GLUT1 and CAIX expressions, indicating a role of MCT1 in the hyperglycolytic and acid-resistant phenotype characteristic of less oxygenated (Pinheiro et al 2011), instead of oxygenated cancer cells as pointed by others (Sonveaux et al 2008).…”

“…This entails the search for new molecular targets in this aggressive group of tumours, and, considering the increased expression of MCT1 in basal-like tumours (Pinheiro et al 2010), as well as recent evidence showing MCTs to be effective anti-cancer targets (Mathupala et al 2004, Colen et al 2006, Fang et al 2006, Sonveaux et al 2008, MCT1 emerges as a promising therapeutic target that needs to be further explored in breast cancer. In this work, we analysed MCT1 and MCT4 expression, as well as the expression of other relevant proteins in cancer metabolism, in a variety of human breast cancer cell lines.…”

“…MCTs belong to a family of 14 members, with isoforms 1-4 being lactate proton symporters that exhibit different affinities for lactate (Halestrap & Meredith 2004). As the isoforms responsible for lactate efflux, MCT1 and MCT4 are probably the most promising in the cancer context and reports on MCT1 and MCT4 upregulation in a variety of tumours are becoming more frequent (Mathupala et al 2004, Fang et al 2006, Koukourakis et al 2006, Pinheiro et al 2008a,b, 2010, 2012. Importantly, we have described association of MCTs, especially MCT1, with poor prognostic variables (Pinheiro et al 2008b, de Oliveira et al 2012, reinforcing the potential of MCT1 as a cancer therapeutic target.…”

Lysyl oxidase-like-1 enhances lung metastasis when lactate accumulation and monocarboxylate transporter expression are involved

“…In this study, LOXL-1 is suggested as a cancer metastasis-associated protein, likely correlated to cancer hypoxic status-associated metastasis. Similarly, MCT1 is significantly increased in breast carcinomas compared with normal breast tissue and, significantly, MCT1 is associated with poor prognostic variables including high-grade tumors (36). MCT1 expression is also associated with advanced gastric carcinoma and lymph node metastasis (37).…”