Genetic variation between cancer patients with the same tumor and intratumor genetic heterogeneity have broadened the complexity of factors that contribute to clinical therapeutic resistance and poor response outcomes. This has made it imperative to identity atypical expressed outliers that influence the maintenance and progression of cancers. We have identified and investigated the spectraplakin protein, Microtubule Actin Cross-Linking Factor 1 (MACF1) which functions as an actin-microfilament and microtubule crosslinker for its role in lung cancers. Genomic data generated by the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) indicate that the MACF1 gene is mutated and/or amplified in ∼15% of squamous lung cancers and 25% of lung cancers, respectively. Further examination with immunohistochemistry expression analysis revealed that MACF1 is highly expressed in several lung cancer subtypes, particularly adenocarcinomas and squamous cell carcinomas, as compared to normal lung tissue. Additionally, functional studies showed that suppression of MACF1 with RNA interference significantly impaired the reproductive capacity of these solid tumors. Taken together, MACF1 represents a unique target with genetic alterations and diagnostic biomarker potential in lung cancers, the leading cause of cancer deaths in the United States.

Citation Format: Najlaa Afghani, Quincy A. Quick. Characterization of the cytoskeletal protein MACF1 in lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4750.