Molecular mechanism of LKB1 in the invasion and metastasis of colorectal cancer.

Abstract

The occurrence of colorectal cancer (CRC) is associated with a variety of oncogenes and tumor‑suppressor genes. As a tumor‑suppressor gene, the liver kinase B1 gene (LKB1, also known as serine/threonine kinase 11, STK11) is closely related to tumor angiogenesis, invasion and metastasis, but its molecular mechanisms remain unclear. The aim of the present study was to investigate the effects of LKB1 on the invasion and metastasis of CRC, and to explore its molecular mechanisms. By detecting the expression of LKB1 in CRC, we can provide a reference index for diagnosing the depth of invasion and lymph node metastasis. Immunohistochemistry results indicated that LKB1 expression was strongly positive in normal colon tissue and that it inhibited the production of CRC. Immunocytochemical staining showed that the expression of LKB1 was significantly decreased in adenocarcinoma and mucinous adenocarcinoma tissues, and this reduced expression induced the invasion and metastasis of CRC. In the present study, LKB1 small interfering RNA (LKB1 siRNA) was transfected into LoVo cells to observe the effect of LKB1 on the invasion and metastasis of CRC. LKB1 silencing decreased the phosphorylation of AMP‑activated protein kinase (p‑AMPK) in its downstream pathway, which increased the phosphorylation of protein kinase B (p‑AKT) and promoted tumor cell proliferation, enhancing the migration and invasion of CRC. The present study also explored the role of metformin in the LKB1 signaling pathway. Metformin inhibits the invasion and metastasis of CRC by activating p‑AMPK, thereby inhibiting the activation of p‑AKT. These results suggest that LKB1 plays an important role in the invasion and metastasis of CRC by activating AMPK, negatively regulating the AKT signaling pathway and regulating gene expression. Mutation or deletion of LKB1 is expected to be a novel therapeutic target or clinical biomarker for the prevention of the invasion and metastasis of CRC.