L1 cell adhesion molecule as a therapeutic target in cancer

SUMMARY

L1 cell adhesion molecule (L1CAM) is the prototype member of the L1-family of closely related neural adhesion molecules. L1CAM is differentially expressed in the normal nervous system as well as pathological tissues and displays a wide range of biological activities. In human malignancies, L1CAM plays a vital role in tumor growth, invasion and metastasis. Recently, increasing evidence has suggested that L1CAM exerts a variety of functions at different steps of tumor progression through a series of signaling pathways. In addition, L1CAM has been identified as a promising target for cancer therapy by using synthetic and natural inhibitors. In this review, we provide an up-to-date overview of the role of L1CAM involved in cancers and the rationale for L1CAM as a novel molecular target for cancer therapy.

KEYWORDS:

• L1 cell adhesion molecule
• cell migration
• signal pathway
• cancer therapy
• prognostic marker

Financial & competing interests disclosure

This work was financially supported by The National Natural Science Foundation of China (81201896 and 81071884), the Key Project of National Health and Planning Commission of the PRC on General Surgery 2012, the Key Project of National Health and Planning Commission of the PRC on Oncology 2013 and The Research Fund for the Doctoral Program of Higher Education of China (20130071110052 and 20110071110065). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• L1CAM is expressed in normal nervous system and pathologic tissues, displays a wide range of biological activities.

• In human malignancies, L1CAM plays a vital role in tumor growth, invasion and metastasis.

• Increasing evidence has suggested that L1CAM exerts a variety of functions at different steps of tumor progression through a series of signaling pathway.

• L1CAM has been identified as a promising drug target for cancers by using synthetic and natural inhibitors.

• L1CAM can signal through two additional mechanisms: ‘forward’ signaling through regulated intramembrane proteolysis such as MAPK/ERK, PI3K/AKT/PKB; ‘reverse’ signaling through the activation of the transcription factor nuclear factor (NF-κB).

• We provided an up-to-date overview of L1CAM in different molecular and biochemical pathways involved in human malignancies.

• We summarized studies on inhibition of L1CAM by means of RNA interference or antibody.

• More in vivo evidence, for example, using both transgenic and xenograft mouse models for various cancers, will help elucidate therapeutic applications for L1CAM.