The Role of LKB1 in Melanoma (2009)

Undergraduates: Kate Bradford, Kim Monahan

Faculty Advisor: Norman Sharpless
Department: Biology

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Melanoma is the most lethal form a skin cancer. It is the only cancer with an increase in incidence over the last three decades, which is still continuing to rise, most likely due to an increase in sun exposure. Activation of the RAS-RAF-ERK pathway is a hallmark of cutaneous melanoma, with approximately 20% of melanomas harboring an activating mutation in N-RAS and 70% of melanomas harboring an activating mutation in B-RAF. Recently, LKB1, a serine-threonine kinase, has been shown to be a downstream target of the B-RAFV600E mutation, causing LKB1 to be phosphorylated; therefore, LKB1 is unable to activate AMPK, which regulates cell growth during stress. It is thought that LKB1 acts as a tumor suppressor by regulating cell growth and proliferation, and that in its absence, tumorigenesis occurs. Here, we studied the expression levels of LKB1 in various human melanoma cell lines and found that LKB1 expression is down-regulated in some cell lines, indicating that LKB1 could contribute to tumorigenesis. We also performed a proliferation assay to see if LKB1 loss plays a role in proliferation; we found that the presence, or absence, of LKB1 does not affect proliferation. This suggests that LKB1 might play another role in the progression of melanoma, such as differentiation or invasion. This work provides evidence that loss of LKB1 function may contribute to the pathogenesis of melanoma.