Abstract
Dysregulation of T cell differentiation protein 2 (MAL2) has been observed in multiple cancers, but its exact role in lung cancer is poorly understood. Here we report a role of MAL2 in accelerating cell proliferation in non-small cell lung cancer (NSCLC). MAL2 expression enhances cell proliferation in both cell and nude mouse models. Mechanistically, overexpression of MAL2 results in the hyper-activation of the MAPK/mTOR signaling pathway in NSCLC cells which leads to active ribosome biogenesis. Importantly, pharmacological inhibition of mTOR or MEK lowered the abundance of PCNA, a marker of tumor cell proliferation, and subsequently suppressed ribosome biogenesis, cell growth and xenograft growth in mouse model. MAL2 upregulation in clinical tumors is also linked to worse prognosis. Overall our data reveal that MAL2 is a potential diagnostic biomarker and targeting the MAL2/MAPK/mTOR signaling pathway may improve therapeutic strategy and efficacy for this subset of NSCLC patients.