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Targeting non-junctional Claudin-1 with monoclonal antibodies to treat hepatocellular carcinoma

ABSTRACT: Targeting non-junctional Claudin-1 with monoclonal antibodies to treat hepatocellular carcinoma

PROVIDER: PRJNA804569 | ENA |

REPOSITORIES: ENA

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Targeting non-junctional Claudin-1 with monoclonal antibodies to treat hepatocellular carcinoma [RNA-seq]

Project description:Targeting non-junctional Claudin-1 with monoclonal antibodies to treat hepatocellular carcinoma [RNA-seq]

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Project description:Abstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Despite new treatment approvals, treatment response and prognosis of patients with advanced HCC remains poor. Claudin-1 (CLDN1) is a membrane protein expressed in tight junctions but also non-junctionally at the basolateral membrane of hepatocytes. While the function of CLDN1 within tight junctions is well characterized, the role of non-junctional (NJ) CLDN1 in HCC remains unexplored. Here we show that targeting NJ-CLDN1 with a humanized monoclonal antibody (mAb) suppresses tumor growth in different pre-clinical models. Mechanistic studies including single cell RNA sequencing of multicellular patient tumorspheres suggest that non-junctional CLDN1 regulates tumor stemness, metabolism and oncogenic signaling with impact on the tumor immune microenvironment. Our results provide the rationale for targeting NJ-CLDN1 in HCC and pave the way to novel therapeutic interventions with NJ-CLDN1 mAbs aimed at improving the limited efficacy of current therapies.

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