Tumor-intrinsic KLRC1 exerts tumor-suppressive functions in colorectal cancer

Colon adenocarcinoma (COAD) represents a prevalent malignant neoplasm within the gastrointestinal tract characterized by significant morbidity and mortality rates, and the majority of patients are in intermediate to advanced stages at the time of diagnosis. Killer cell lectin-like receptor C1 gene (KLRC1) is an inhibitory receptor in the NKG2 receptor family that can be recognized by HLA-E, thereby inhibiting cytotoxic activity and cytokine secretion from NK cells. However, little is known about its function in various cancers, including COAD. In the present study, we revealed that reduced expression of KLRC1 in COAD correlates with adverse prognosis, suboptimal histological characteristics, and more advanced pathological staging. In addition, KLRC1 expression independently predicted progression in COAD patients. According to the functional enrichment analysis, KLRC1 has been implicated in signaling pathways related to the immune response and cellular proliferation. In addition, we verified that KLRC1 was down-regulated in COAD cell lines and that the overexpression of KLRC1 significantly reduced the migration, invasion, and proliferation capacities and xenograft tumor growth of COAD cell lines. Our study elucidates that KLRC1 is a novel prognostic marker and a therapeutic target for COAD.