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MTA1 is a novel regulator of autophagy that induces tamoxifen resistance in breast cancer cells
Lee, Min-Ho,Koh, Dahae,Na, Hyelin,Ka, Na-Lee,Kim, Seungsu,Kim, Hyeon-Ji,Hong, Sungyoul,Shin, Young Kee,Seong, Je Kyung,Lee, Mi-Ock TaylorFrancis 2018 AUTOPHAGY Vol.14 No.5
<P><B>ABSTRACT</B></P><P>Tamoxifen is commonly used to treat patients with ESR/ER-positive breast cancer, but its therapeutic benefit is limited by the development of resistance. Recently, alterations in macroautophagy/autophagy function were demonstrated to be a potential mechanism for tamoxifen resistance. Although MTA1 (metastasis-associated 1) has been implicated in breast tumorigenesis and metastasis, its role in endocrine resistance has not been studied. Here, we report that the level of MTA1 expression was upregulated in the tamoxifen resistant breast cancer cell lines MCF7/TAMR and T47D/TR, and knockdown of MTA1 sensitized the cells to 4-hydroxytamoxifen (4OHT). Moreover, knockdown of MTA1 significantly decreased the enhanced autophagy flux in the tamoxifen resistant cell lines. To confirm the role of MTA1 in the development of tamoxifen resistance, we established a cell line, MCF7/MTA1, which stably expressed MTA1. Compared with parental MCF7, MCF7/MTA1 cells were more resistant to 4OHT-induced growth inhibition in vitro and in vivo, and showed increased autophagy flux and higher numbers of autophagosomes. Knockdown of ATG7 or cotreatment with hydroxychloroquine, an autophagy inhibitor, restored sensitivity to 4OHT in both the MCF7/MTA1 and tamoxifen resistant cells. In addition, AMP-activated protein kinase (AMPK) was activated, probably because of an increased AMP:ATP ratio and decreased expression of mitochondrial electron transport complex components. Finally, publicly available breast cancer patient datasets indicate that MTA1 levels correlate with poor prognosis and development of recurrence in patients with breast cancer treated with tamoxifen. Overall, our findings demonstrated that MTA1 induces AMPK activation and subsequent autophagy that could contribute to tamoxifen resistance in breast cancer.</P>
Seungsue Lee,Hyun Ah Kang,Seong-il Eyun 한국미생물학회 2020 The journal of microbiology Vol.58 No.9
Cryptococcus neoformans is an opportunistic fungal pathogen causing cryptococcal meningoencephalitis. Interestingly, the cell wall of C. neoformans contains chitosan, which is critical for its virulence and persistence in the mammalian host. C. neoformans (H99) has three chitin deacetylases (CDAs), which convert chitin to chitosan. Herein, the classification of the chitin-related protein (CRP) family focused on cryptococcal CDAs was analyzed by phylogenetics, evolutionary pressure (dN/dS), and 3D modeling. A phylogenetic tree of 110 CRPs revealed that they can be divided into two clades, CRP I and II with bootstrap values (> 99%). CRP I clade comprises five groups (Groups 1–5) with a total of 20 genes, while CRP II clade comprises sixteen groups (Groups 6–21) with a total of 90 genes. CRP I comprises only fungal CDAs, including all three C. neoformans CDAs, whereas CRP II comprises diverse CDAs from fungi, bacteria, and amoeba, along with other carbohydrate esterase 4 family proteins. All CDAs have the signal peptide, except those from group 11. Notably, CDAs with the putative O-glycosylation site possess either the glycosylphosphatidylinositol (GPI)-anchor motif for CRP I or the chitin-binding domain (CBD) for CRP II, respectively. This evolutionary conservation strongly indicates that the O-glycosylation modification and the presence of either the GPI-anchor motif or the chitin-binding domain is important for fungal CDAs to function efficiently at the cell surface. This study reveals that C. neoformans CDAs carrying GPI anchors have evolved divergently from fungal and bacterial CDAs, providing new insights into evolution and classification of CRP family.
Granular Cell Tumor: An Unusual Cause of Common Peroneal Neuropathy
Lee Juwon,Park Jintae,Jeong Seungsu,Noh Jung Ho,Kang Gu,Baek Sora 대한근전도전기진단의학회 2023 대한근전도 전기진단의학회지 Vol.25 No.2
Granular cell tumors, also known as Abrikossoff’s tumors, are rare soft-tissue tumors, and their occurrence in the peripheral nerves has been very rarely reported. We present the case of a 35-year-old woman with common peroneal neuropathy due to a granular cell tumor, who complained of foot dragging. Common peroneal neuropathy was confirmed by electrophysiology. The tumor mass was observed using ultrasonography and magnetic resonance imaging. The tumor was surgically excised, the tumor cells stained positive for S-100, and eosinophilic granular cytoplasm was observed using microscopy. To the best of our knowledge, this is the first report of a granular cell tumor involving the common peroneal nerve.