Inhibition of autophagy mitigates cell migration and invasion in thyroid cancer

甲状腺间变性癌 自噬 医学 下调和上调 CD44细胞 癌症研究 甲状腺癌 癌症干细胞 死孢子体1 细胞培养 滤泡状甲状腺癌 癌症 癌细胞 细胞生物学 细胞 细胞凋亡 细胞迁移 生物 内科学 甲状腺乳突癌 生物化学 基因 遗传学
作者
Tammy M. Holm,Z. Christine Bian,Kanakaraju Marumudi,Jun‐Lin Guan
出处
期刊:Surgery [Elsevier BV]
卷期号:171 (1): 235-244 被引量:8
标识
DOI:10.1016/j.surg.2021.08.024
摘要

Autophagy is a highly conserved process for maintaining cellular homeostasis. Upregulation of autophagy promotes metastasis by promoting the cancer stem cell state while also stimulating tumor cell migration and invasion. We hypothesized that autophagy upregulation would be critical for cancer stem cell maintenance as well as cellular migration and invasion in thyroid cancer.Validated papillary (MDA-T32, MDA-T68), follicular (FTC-133), and anaplastic (ATC-8505c) human thyroid cancer cell lines in culture were first assessed for autophagic capacity after bafilomycin clamping. Cancer stem cells were quantified by flow cytometry for aldehyde dehydrogenase and thyrosphere formation assay. Scratch migration and Matrigel invasion assays were performed in the presence of known autophagy inhibitors: Lys05, chloroquine, and FIP200siRNA.Autophagy activity was observed across all cell lines. Thyrosphere formation, aldehyde dehydrogenase activity, and CD44 expression were reduced with inhibition of autophagy in MDA-T32, MDA-T68, FTC-133, and 8505c cells. Similarly, cell migration and invasion were attenuated: 42% (FIP200siRNA), 78% (Lys05), P < .001 in MDA-T32 cells; 54% (FIP200siRNA), 67% (Lys05), P < .001 in MDA-T68 cells; 73% (FIP200siRNA), 71% (Lys05), P < .001) in FTC-133 cells; and 60% (FIP200siRNA), 90% (Lys05), P < .001 in 8505c cells. Invasion assays demonstrated a 73%, 39%, 75%, and 65.1% reduction in the presence of Lys05 in T32, T68, FTC-133, and 8505c cells, respectively. We observed similar reductions in invasion with FIP200siRNA: 61%, 62%, 55%, and 81.4% in T32, T68, FTC-133, and 8505c cells.Autophagy is upregulated across multiple thyroid cancer subtypes. In thyroid cancer cell lines, inhibition of autophagy attenuates cancer stem cell viability, cell migration, and invasion suggesting a role for autophagy in the progression of thyroid cancer. Greater understanding of autophagy regulation in thyroid cancer will aid in developing targeted therapeutics.
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