Pathway of the Month
Axl Receptor Axis: A New Therapeutic Target in Lung Cancer
Axl belongs to the TAM family of receptor tyrosine kinases, which consists of Tyro3, Axl, and Mer. All three family members have similar structures and share a number of ligands, including the vitamin K–dependent ligands growth arrest protein 6 (Gas6) and protein S. In normal tissues, TAM receptor tyrosine kinases contribute to immune response regulation, including clearance of apoptotic cells and inhibition of cytotoxic immune activation in response to apoptosis. When cells undergo apoptosis, the polarity of the plasma membrane lipid bilayer is altered, externalizing the anionic phospholipid phosphatidylserine (PS).TGF-² Signaling and the Role of Inhibitory Smads in Non-small Cell Lung Cancer
The signaling pathway mediated by transforming growth factor-² (TGF-²) participates in various biologic processes, including cell growth, differentiation, angiogenesis, apoptosis, and extracellular matrix remodeling. In the context of cancer, TGF-² signaling can inhibit tumor growth in early-stage tumors. However, in late-stage tumors, the very same pathway promotes tumor invasiveness and metastasis. This paradoxical effect is mediated through similar to mothers against decapentaplegic or Smad protein dependent and independent mechanisms and provides an opportunity for targeted cancer therapy.RBM5 as a Putative Tumor Suppressor Gene for Lung Cancer
RBM5 is one member of a group of structurally related genes that includes RBM6 and RBM10. RBM10 maps to Xp11.23, and one allele is inactivated as a result of X chromosome inactivation. Both RBM5 and RBM6 map to 3p21.3, a tumor suppressor region that experiences loss of heterozygosity in the majority of lung cancers. Overexpression of RBM5, which encodes an RNA-binding protein involved in the regulation of alternative splicing and retards ascites associated tumor growth in immunocompromised mice, a phenomenon that may be related to an associated ability to modulate apoptosis.TGF-² Signaling Pathway in Lung Adenocarcinoma Invasion
The histologic distinction between bronchioloalveolar carcinoma and other adenocarcinomas is tissue invasion. The clinical importance of lung adenocarcinoma invasion is supported by several recent studies indicating that the risk of death in nonmucinous bronchioloalveolar carcinoma is significantly lower than that of pure invasive tumors and in tumors with greater than 0.5 cm of fibrosis or linear invasion. Using microarray gene expression profiling of human tumors, dysregulation of transforming growth factor-² signaling was identified as an important mediator of tumor invasion.Acetylcholine Receptor Pathway and Lung Cancer
Genome-wide association studies revealed chromosome regions 15q24-25 were associated with a higher risk for development of lung cancer. The 15q24-25 region encompasses the nicotinic acetylcholine receptor subunit genes (nAchR ±3, ±5, and ²4) that play a role in nicotine addiction. This review reports information of the acetylcholine receptor and lung cancer. In patients diagnosed with smoking-related lung cancer and who continue smoking, a negative correlation with lung cancer survival has been shown.
