【佳學(xué)基因檢測(cè)】基因檢測(cè)神經(jīng)元蛋白闡述促進(jìn)直腸癌進(jìn)展的靶標(biāo)

基因變異引起的腫瘤惡化的原理

學(xué)習(xí)記錄《J Exp Clin Cancer Res》在. 2022 Sep 2;41(1):266.發(fā)表了一篇題目為《神經(jīng)元蛋白 Neuroligin 1 通過(guò)調(diào)節(jié) APC/β-catenin 通路促進(jìn)結(jié)直腸癌進(jìn)展》腫瘤靶向藥物治療基因檢測(cè)臨床研究文章。該研究由Margherita Pergolizzi , Laura Bizzozero , Federica Maione, Elena Maldi, Claudio Isella, Marco Macagno, Elisa Mariella, Alberto Bardelli, Enzo Medico, Caterina Marchiò, Guido Serini, Federica Di Nicolantonio, Federico Bussolino, Marco Arese 等完成。促進(jìn)了腫瘤的正確治療選擇與直腸癌惡化的作用靶點(diǎn)，基因檢測(cè)結(jié)果的應(yīng)再次豐富全面。

腫瘤靶向藥物及正確治療臨床研究?jī)?nèi)容關(guān)鍵詞：

轉(zhuǎn)移相關(guān)基因,直腸癌,總生存期,預(yù)后

腫瘤靶向治療基因檢測(cè)臨床應(yīng)用結(jié)果

結(jié)直腸癌惡化進(jìn)展的基因檢測(cè)研究背景：結(jié)直腸癌 (CRC) 在轉(zhuǎn)移階段診斷時(shí)仍然很大程度上無(wú)法治好。盡管近年來(lái)針對(duì)這種疾病的正確醫(yī)學(xué)取得了一些進(jìn)展，但仍然非常需要新的分子靶點(diǎn)以及預(yù)后/預(yù)測(cè)標(biāo)志物。 腫瘤的基因解碼研究表明Neuroligin 1 (NLGN1) 是一種跨膜蛋白，在突觸處與腫瘤抑制性腺瘤性息肉病 (APC) 相互作用，APC 與 CRC 的發(fā)病機(jī)制密切相關(guān)，是 WNT/β-catenin 通路的關(guān)鍵參與者。結(jié)直腸癌惡化進(jìn)展的基因檢測(cè)研究方法：在對(duì)人類 CRC 樣本進(jìn)行 NLGN1 表達(dá)研究后，在結(jié)直腸癌惡化進(jìn)展的基因檢測(cè)研究中，基因解碼基因檢測(cè)使用體外和體內(nèi)方法來(lái)研究 CRC 細(xì)胞外滲和轉(zhuǎn)移形成能力。在分子水平上，研究了 APC 和 NLGN1 在癌癥背景下的功能聯(lián)系。結(jié)直腸癌惡化進(jìn)展的基因檢測(cè)研究結(jié)果：這里基因解碼基因檢濁顯示 NLGN1 在人類結(jié)直腸腫瘤中表達(dá)，包括侵襲性遷移（出芽）的單個(gè)腫瘤細(xì)胞簇和血管栓子?；蚪獯a基因檢測(cè)發(fā)現(xiàn) NLGN1 在體外促進(jìn) CRC 細(xì)胞穿過(guò)內(nèi)皮單層（即跨內(nèi)皮遷移或 TEM），以及兩種小鼠模型中的細(xì)胞外滲/肺侵襲和不同的器官轉(zhuǎn)移。從機(jī)制上講，NLGN1 促進(jìn) APC 定位到細(xì)胞膜并與該蛋白的一些同種型共免疫沉淀，刺激 β-連環(huán)蛋白易位至細(xì)胞核，上調(diào)間充質(zhì)標(biāo)志物和 WNT 靶基因，并在 CRC 細(xì)胞系中誘導(dǎo)“EMT 表型”。總之，結(jié)直腸癌的惡化機(jī)制基因解碼發(fā)現(xiàn)了一種新的 CRC 侵襲性調(diào)節(jié)劑，它影響該疾病的關(guān)鍵發(fā)病途徑，并可能代表一種新的治療靶點(diǎn)，并具有繼承神經(jīng)生物學(xué)領(lǐng)域大量知識(shí)的額外好處。神經(jīng)素 1； WNT通路；內(nèi)滲/外滲；轉(zhuǎn)移;腫瘤出芽。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國(guó)際數(shù)據(jù)庫(kù)描述：

Background: Colorectal cancer (CRC) remains largely incurable when diagnosed at the metastatic stage. Despite some advances in precision medicine for this disease in recent years, new molecular targets, as well as prognostic/predictive markers, are highly needed. Neuroligin 1 (NLGN1) is a transmembrane protein that interacts at the synapse with the tumor suppressor adenomatous polyposis Coli (APC), which is heavily involved in the pathogenesis of CRC and is a key player in the WNT/β-catenin pathway.Methods: After performing expression studies of NLGN1 on human CRC samples, in this paper we used in vitro and in vivo approaches to study CRC cells extravasation and metastasis formation capabilities. At the molecular level, the functional link between APC and NLGN1 in the cancer context was studied.Results: Here we show that NLGN1 is expressed in human colorectal tumors, including clusters of aggressive migrating (budding) single tumor cells and vascular emboli. We found that NLGN1 promotes CRC cells crossing of an endothelial monolayer (i.e. Trans-Endothelial Migration or TEM) in vitro, as well as cell extravasation/lung invasion and differential organ metastatization in two mouse models. Mechanistically, NLGN1 promotes APC localization to the cell membrane and co-immunoprecipitates with some isoforms of this protein stimulates β-catenin translocation to the nucleus, upregulates mesenchymal markers and WNT target genes and induces an "EMT phenotype" in CRC cell lines CONCLUSIONS: In conclusion, we have uncovered a novel modulator of CRC aggressiveness which impacts on a critical pathogenetic pathway of this disease, and may represent a novel therapeutic target, with the added benefit of carrying over substantial knowledge from the neurobiology field.Keywords: APC; Neuroligin 1; WNT pathway; intravasation/extravasation; metastasis; tumor budding.