Cancer cell mRNA localization during metastasis

Monday, September 22, 2014 — Poster Session I
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NCI	BIOENG-5

Authors

• SM Hamilla
• S Mili

Abstract

Localized mRNAs play an important role in cellular migration and localize to cellular protrusions and become disrupted in cancer progression. In one pathway, the tumor suppressor protein, adenomatous polyposis coli (APC) targets RNAs to cell protrusions. APC associates with many RNAs in protrusive areas, including Ddr2, Rab13, and Pkp4. Additionally, cancer cell behavior is affected by the mechanical properties of the substrate and they modulate their gene expression in response to these extracellular cues. We used the MCF10A cell series, a breast cancer progression model composed of four different cell lines representing different stages of pre-malignant to invasive transformation to investigate mRNA localization and how it is affected by substrate stiffness. By using in situ hybridization, and polyacrylamide gels of varying stiffness, we were able to observe APC associated mRNA localization of mRNAs Pkp4, Rab13, and Ddr2. We find that the accumulation of candidate mRNAs at the cell periphery increases with increasing metastatic transformation in the MCF10A cell series. Additionally, we observe that cytoplasmic mRNAs are more localized on stiff 280kPa and glass substrates compared to soft 0.87kPa substrates.

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