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Kanker mikro dan respon stres endoplasma Claudia Giampietri, Simonetta Petrungaro, Silvia Conti, Antonio Facchiano, Antonio Filippini, dan Elio Ziparo Mediator inflamasi. (Tahunan 2015): dari ilmu InfoTrac koleksi 2017. DOI: http://dx.doi.org/10.1155/2015/417281 Copyright: Hak cipta 2015 Hindawi penerbitan Corp http://www.hindawi.com/ Abstrak: Kondisi stres yang berbeda seperti hipoksia, kekurangan gizi, perubahan pH atau mengurangi pembuluhnya, berpotensi dapat bertindak sebagai faktor membatasi pertumbuhan sel-sel tumor, Aktifkan respon dibentangkan protein (UPR). UPR terlibat dalam pertumbuhan tumor dan adaptasi terhadap lingkungan yang parah dan umumnya cytoprotective di kanker. Review hadir menjelaskan mekanisme molekul yang mendasari UPR dan dapat mempromosikan kelangsungan hidup dan proliferasi kanker. Peranan penting dari UPR aktivasi dalam promosi pertumbuhan tumor dibahas secara rinci untuk beberapa paradigmatik tumor seperti kanker prostat dan melanoma. Teks lengkap: 1. Pendahuluan Selular lingkungan yang terus berubah; dengan demikian fisiologis respon adaptif muncul untuk mempertahankan homeostasis keseimbangan dan jaringan selular secara keseluruhan. Dalam kerangka tersebut, banyak cara telah berevolusi untuk memungkinkan adaptasi optimal untuk lingkungan stres atau, di bawah kondisi ekstrim kerusakan, untuk menghapus sel-sel yang berpenyakit dan mencegah keracunan [1]. The endoplasmic reticulum (ER) is the intracellular organelle controlling intracellular [Ca.sup.2+] homeostasis, lipid synthesis, and protein folding. Protein folding occurring in the ER is extremely sensitive to environmental changes regarding redox state, nutrient and [Ca.sup.2+] levels, protein synthesis rate, occurrence of pathogens or inflammatory stimuli, altering protein folding, and ultimately causing accumulation of unfolded or misfolded proteins. This condition is generally known as "ER stress" [2] and a sensitive surveillance mechanism ensures degradation of misfolded proteins [3] preventing entry of misfolded proteins in the secretory pathway. When ER stress occurs, ER functions are altered and a number of molecular actions, collectively named "unfolded protein response" (UPR), are activated to counteract the ER stress-associated damages. The UPR has a dual function: it mitigates damage associated with ER stress and, if this is not possible, it activates apoptosis [1]. ER stress response/UPR signaling pathways are activated in primary solid tumors as a result of cell-intrinsic defects, such as dysregulation of protein synthesis, folding, and secretion, and also as a consequence of microenvironment changes. Solid tumors microenvironment differs from normal tissues microenvironment, the former being characterized by nutrient (e.g., glucose) deprivation, low pH, hypoxia, and imbalance between production and removal of reactive oxygen species (i.e., oxidative stress) [4, 5]. Semua faktor-faktor lingkungan seperti berkontribusi ER stres dan sel-sel kanker memilih cara yang efektif untuk beradaptasi dan mencegah ER diinduksi stres apoptosis [6, 7]. Penelitian terbaru telah diselidiki secara rinci cara yang berbeda digunakan oleh sel-sel kanker, kondisi stres ER, untuk satu pensinyalan kematian sel ER-terkait dan untuk mempromosikan pertumbuhan tumor [8, 9]. Dalam review hadir jalur UPR dikenal dirangkum; kemudian stres ER berbeda bertindak dalam kanker mikro dilaporkan dan akhirnya berubah ER stres tanggapan di kanker dijelaskan, menekankan implikasi terapeutik mereka mungkin. [GAMBAR 1 DIHILANGKAN] 2. respon stres ER Respon dibentangkan protein (UPR) adalah respon selular menghubungkan UGD inti [10]. Ini mewakili selular kunci yang menandakan proses diselidiki sejak awal tahun sembilan puluhan dalam ragi [11,12]. As shown in Figure 1, three ER-associated proteins are key players of UPR, namely, Pancreatic ER Kinase (PERK) [13], Inositol-Requiring Enzyme 1 (IRE1) [14], and Activating Transcription Factor 6 (ATF6) [15]. Under normal conditions, such three transmembrane proteins are bound and inactivated by a chaperone, Glucose Regulated Protein 78 (BiP, also known as GRP78) [16]. As response to ER stress, BiP dissociates from the UPR sensors to allow their proper signaling [17]. The activation of the ER stress sensors and of their downstream targets halts new proteins transcription and increases the synthesis of molecular chaperones. As a first consequence, the UPR promotes cell survival by enhancing ER ability to fold proteins and preventing further protein accumulation that might exacerbate the ER damage. If such response is not sufficient and the stress persists, the UPR leads to apoptosis [18]. Although the exact molecular mechanisms involved are not known, several evidences suggest that cell death induced by ER stress requires continuous signals exchange between ER and mitochondria [19]. This communication depends on the presence of a physical link between the two organelles, represented by specific contact
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