Abstract
There are two major groups of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLCs can be further separated into three different categories: lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Pulmonary adenocarcinomas represent nearly half of all lung cancer cases and are known to be caused by smoking, certain occupational exposures, and specific genetic mutations. Scientists have noticed that most NSCLCs are driven by defects in the following genes: EGFR, BRAF, ALK, MET, and HER. Abnormalities in the STK11/LKB1 gene have also been shown to induce lung adenocarcinoma. LKB1-deficient cancer cells contain an overactive AMPK “energy sensor,” which inhibits cellular death and promotes glucose, lipid, and protein synthesis via the mTOR protein complex. Studies have also discovered that the loss of STK11/LKB1 favors oncogenesis by creating an immunosuppressive environment for tumors to grow and accelerate events such as angiogenesis, epithelial-mesenchymal transition (EMT), and cell polarity destabilization. STK11/LKB1-mutant lung cancers are currently treated with radiotherapy with or without chemotherapy. Recent clinical trials studying the effects of glutaminase inhibitors, mTOR inhibitors, and anti-PD-L1 therapy in lung cancer patients have yielded promising results. This narrative review provides an overview of the STK11/LKB1 gene and its role in cancer development. Additionally, a summary of the LKB1/APMK/mTOR is provided.
Highlights
BackgroundNon-small cell lung cancers (NSCLCs) represent approximately 85% of all lung cancer cases and can be subdivided into three major groups: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma [1]
Most lung cancer cases are linked to cigarette smoking, epidemiologic studies suggest that approximately 10% of all lung cancer patients have no smoking history [2]
serine/threonine kinase 11 (STK11)/liver kinase B1 (LKB1) mutations are more prevalent in lung adenocarcinomas but are found in pulmonary squamous cell carcinoma and large cell adenocarcinoma [35]
Summary
Non-small cell lung cancers (NSCLCs) represent approximately 85% of all lung cancer cases and can be subdivided into three major groups: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma [1]. Sterol regulatory element-binding protein 1 (SREBP1) tightly controls fatty acid and cholesterol synthesis by regulating the expression of different proteins such as ACC, fatty acid synthase (FASN), and ATP citrate lyase (ACYL) [33,34] Both ACC and SREBP1 are normally inhibited by AMPK, but in LKB-1 deficient cells, these enzymes are continuously active and permit the accumulation of lipid [29]. STK11/LKB1 mutations are more prevalent in lung adenocarcinomas but are found in pulmonary squamous cell carcinoma and large cell adenocarcinoma [35] These mutations routinely co-occur with KRAS mutations and seem to be associated with a decreased overall survival due to their ability to create aggressive tumors with metastatic features [35,36].
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