GCC2通过维持高尔基体完整性和刺激EGFR信号通路促进非小细胞肺癌癌症进展-动脉网

GCC2 promotes non-small cell lung cancer progression by maintaining Golgi apparatus integrity and stimulating EGFR signaling pathways

Nature 等信源发布 2024-11-22 20:48

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AbstractFundamental changes in intracellular processes, such as overactive growth signaling pathways, are common in carcinomas and are targets of many cancer therapeutics. GRIP and coiled-coil containing 2 (GCC2) is a trans-Golgi network (TGN) golgin maintaining Golgi apparatus structure and regulating vesicle transport.

摘要细胞内过程的基本变化，如过度活跃的生长信号通路，在癌症中很常见，并且是许多癌症治疗的目标。含有2（GCC2）的GRIP和卷曲螺旋是一种反式高尔基网络（TGN）高尔金，可维持高尔基体结构并调节囊泡运输。

Here, we found an aberrant overexpression of GCC2 in non-small cell lung cancer (NSCLC) and conducted shRNA-mediated gene knockdown to investigate the role of GCC2 in NSCLC progression. shRNA-mediated GCC2 knockdown suppressed NSCLC cell growth, migration, stemness, and epithelial-mesenchymal transition (EMT) in vitro and tumor growth in vivo.

在这里，我们发现GCC2在非小细胞肺癌（NSCLC）中异常过表达，并进行了shRNA介导的基因敲除，以研究GCC2在NSCLC进展中的作用。shRNA介导的GCC2敲低在体外抑制NSCLC细胞生长，迁移，干性和上皮-间质转化（EMT）以及体内肿瘤生长。

In addition, GCC2 knockdown suppressed cancer cell exosome secretion and the oncogenic capacity of cancer cell-derived exosomes. Mechanistically, GCC2 inhibition decreased epidermal growth factor receptor (EGFR) expression and downstream growth and proliferation signaling. Furthermore, GCC2 inhibition compromised Golgi structural integrity in cancer cells, indicating a functional role of GCC2 in regulating intracellular trafficking and signaling to promote lung cancer progression.

此外，GCC2敲低抑制癌细胞外泌体分泌和癌细胞衍生的外泌体的致癌能力。从机制上讲，GCC2抑制降低了表皮生长因子受体（EGFR）的表达以及下游的生长和增殖信号传导。此外，GCC2抑制损害了癌细胞中高尔基体的结构完整性，表明GCC2在调节细胞内运输和信号传导以促进肺癌进展中的功能作用。

Together, these findings suggest GCC2 as a potential therapeutic target for the treatment of NSCLC..

总之，这些发现表明GCC2是治疗NSCLC的潜在治疗靶点。。

IntroductionLung cancer, the leading cause of cancer-related deaths in the United States, is estimated to be responsible for 127,070 deaths in 2023, which is far more than any other cause of cancer mortality 1. More than 80% of lung cancer cases are classified as non-small cell lung cancer (NSCLC), and the 5-year relative survival rate for NSCLC is 23% 2.

。超过80%的肺癌病例被归类为非小细胞肺癌（NSCLC），NSCLC的5年相对生存率为23%2。

While recent advances in diagnosis and treatment options have improved the outlook on lung cancer, prognosis remains unfavorable for lung cancer patients. Therefore, understanding the molecular mechanisms of lung cancer progression and developing novel therapeutic targets are crucial to improve patient survival.GRIP and coiled-coil containing 2 (GCC2) is a trans-Golgi network (TGN) golgin with a conserved GRIP domain and an extensive coiled-coil domain to form rod-like, α-helical homodimers.

虽然诊断和治疗选择的最新进展改善了肺癌的前景，但预后仍然不利于肺癌患者。因此，了解肺癌进展的分子机制和开发新的治疗靶点对于提高患者生存率至关重要。含有2（GCC2）的GRIP和卷曲螺旋是一种反式高尔基网络（TGN）高尔金，具有保守的GRIP结构域和广泛的卷曲螺旋结构域，可形成棒状α-螺旋同型二聚体。

GCC2 protein is involved in vesicle trafficking and the maintenance of Golgi apparatus structure 3. For instance, GCC2 has been shown to mediate Rab9-dependent vesicle tethering and recycling of mannose 6-phosphate receptors from late endosomes to Golgi 4. In addition, GCC2 has a functional domain required for maintenance of Golgi structure 5.

GCC2蛋白参与囊泡运输和高尔基体结构的维持3。例如，已显示GCC2介导Rab9依赖性囊泡束缚和甘露糖6-磷酸受体从晚期内体到高尔基体4的再循环。此外，GCC2具有维持高尔基体结构5所需的功能域。

The Golgi apparatus is a dynamic organelle involved in anterograde and retrograde vesicle trafficking, cargo sorting and secretion, and cellular processes, including mitosis, cell polarity and motility, autophagy, apoptosis, and inflammation 6,7,8. Alterations in Golgi apparatus structure and Golgi-mediated processes, which involves golgins, have been linked to cancer growth and metastases 9,10,11,12.

高尔基体是一种动态细胞器，参与顺行和逆行囊泡运输，货物分选和分泌以及细胞过程，包括有丝分裂，细胞极性和运动性，自噬，细胞凋亡和炎症6,7,8。。

For example, our previous study revealed increased exosome secretion and elevated GCC2 expression in both NSCLC patient plasmas derived from various pathological stages and NSCLC cell lines, sug.

例如，我们之前的研究显示，来自不同病理阶段的NSCLC患者血浆和NSCLC细胞系sug的外泌体分泌增加，GCC2表达升高。

Data availability

数据可用性

All data generated or analysed during this study are included in this published article and its Supplementary Information files.

本研究期间生成或分析的所有数据均包含在本文及其补充信息文件中。

ReferencesSiegel, R. L. et al. Cancer statistics, 2023. Ca Cancer J Clin 73(1), 17–48 (2023).Article

ReferenceSiegel，R.L.等人，《癌症统计》，2023年。Ca癌症J临床73（1），17-48（2023）。文章

PubMed

Google Scholar

谷歌学者

Schabath, M. B. & Cote, M. L. Cancer progress and priorities: lung cancer. Cancer epidemiology, biomarkers & prevention 28(10), 1563–1579 (2019).Article

Schabath，M.B。和Cote，M.L。癌症进展和优先事项：肺癌。癌症流行病学，生物标志物与预防28（10），1563-1579（2019）。文章

Google Scholar

谷歌学者

Derby, M. C. et al. The trans-Golgi network golgin, GCC185, is required for endosome-to-Golgi transport and maintenance of Golgi structure. Traffic 8(6), 758–773 (2007).Article

Derby，M.C。等人。反式高尔基体网络高尔基体GCC185是内体到高尔基体运输和维持高尔基体结构所必需的。交通8（6），758–773（2007）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Reddy, J. V. et al. A functional role for the GCC185 golgin in mannose 6-phosphate receptor recycling. Molecular biology of the cell 17(10), 4353–4363 (2006).Article

Reddy，J.V.等人。GCC185高尔金在甘露糖6-磷酸受体再循环中的功能作用。细胞的分子生物学17（10），4353-4363（2006）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Brown, F. C., Schindelhaim, C. H. & Pfeffer, S. R. GCC185 plays independent roles in Golgi structure maintenance and AP-1–mediated vesicle tethering. Journal of Cell Biology 194(5), 779–787 (2011).Article

Brown，F.C.，Schindelhaim，C.H。＆Pfeffer，S.R。GCC185在高尔基体结构维持和AP-1介导的囊泡束缚中起独立作用。《细胞生物学杂志》194（5），779-787（2011）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Millarte, V. and H. Farhan, The Golgi in cell migration: regulation by signal transduction and its implications for cancer cell metastasis. The Scientific World Journal, 2012. 2012.Lamb, C. A., Yoshimori, T. & Tooze, S. A. The autophagosome: origins unknown, biogenesis complex. Nature reviews Molecular cell biology 14(12), 759–774 (2013).Article .

Millarte，V。和H.Farhan，《高尔基体在细胞迁移中的作用：信号转导的调节及其对癌细胞转移的影响》。《科学世界杂志》，2012年。。《自然评论》分子细胞生物学14（12），759-774（2013）。文章。

CAS

中科院

PubMed

Google Scholar

谷歌学者

Makhoul, C., Gosavi, P. & Gleeson, P. A. The Golgi architecture and cell sensing. Biochemical Society Transactions 46(5), 1063–1072 (2018).Article

Makhoul，C.，Gosavi，P。＆Gleeson，P.A。高尔基体结构和细胞传感。生物化学学会学报46（5），1063-1072（2018）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Bajaj, R. et al. Dance of The Golgi: Understanding Golgi Dynamics in Cancer Metastasis. Cells 11(9), 1484 (2022).Article

。细胞11（9），1484（2022）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bui, S., et al., Adaptation of the Golgi Apparatus in Cancer Cell Invasion and Metastasis. Frontiers in Cell and Developmental Biology, 2021. 9.Zhang, X., Alterations of Golgi Structural Proteins and Glycosylation Defects in Cancer. Frontiers in Cell and Developmental Biology, 2021. 9.Kulkarni-Gosavi, P., Makhoul, C.

Bui，S。等人，高尔基体在癌细胞侵袭和转移中的适应性。细胞与发育生物学前沿，2021年。9.Zhang，X.，癌症中高尔基体结构蛋白的改变和糖基化缺陷。细胞与发育生物学前沿，2021年。9.Kulkarni-Gosavi，P.，Makhoul，C。

& Gleeson, P. A. Form and function of the Golgi apparatus: scaffolds, cytoskeleton and signalling. FEBS letters 593(17), 2289–2305 (2019).Article .

&Gleeson，P.A。高尔基体的形式和功能：支架，细胞骨架和信号传导。FEBS信函593（17），2289–2305（2019）。文章。

CAS

中科院

PubMed

Google Scholar

谷歌学者

Jeong, H. et al. Gcc2 as a new early diagnostic biomarker for non-small cell lung cancer. Cancers 13(21), 5482 (2021).Article

Jeong，H。等人。Gcc2作为非小细胞肺癌的新早期诊断生物标志物。癌症13（21），5482（2021）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Tu, X. et al. Interruption of post-Golgi STING trafficking activates tonic interferon signaling. Nature communications 13(1), 6977 (2022).Article

Tu，X。等人。高尔基体STING后运输的中断激活了强直性干扰素信号传导。自然通讯13（1），6977（2022）。文章

ADS

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Qin, J. et al. Rare GCC2-ALK fusion G13: A20 detected by next generation sequencing in non-small cell lung cancer patients and treatment response. Translational Cancer Research 8(5), 2187 (2019).Article

。转化癌症研究8（5），2187（2019）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Jiang, J. et al. GCC2-ALK as a targetable fusion in lung adenocarcinoma and its enduring clinical responses to ALK inhibitors. Lung Cancer 115, 5–11 (2018).Article

Jiang，J。等人。GCC2-ALK作为肺腺癌的靶向融合物及其对ALK抑制剂的持久临床反应。肺癌115,5-11（2018）。文章

PubMed

Google Scholar

谷歌学者

Scott, K. L. & Chin, L. Signaling From the Golgi: Mechanisms and Models for Golgi Phosphoprotein 3–Mediated Oncogenesis. Clinical Cancer Research 16(8), 2229–2234 (2010).Article

Scott，K.L。和Chin，L。来自高尔基体的信号传导：高尔基体磷蛋白3介导的肿瘤发生的机制和模型。临床癌症研究16（8），2229-2234（2010）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Scott, K. L. et al. GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer. Nature 459(7250), 1085–1090 (2009).Article

Scott，K.L.等人GOLPH3调节癌症中的mTOR信号传导和雷帕霉素敏感性。《自然》459（7250），1085–1090（2009）。文章

ADS

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ye, Q.-H. et al. GOLM1 modulates EGFR/RTK cell-surface recycling to drive hepatocellular carcinoma metastasis. Cancer cell 30(3), 444–458 (2016).Article

Ye，Q.-H.等人，GOLM1调节EGFR/RTK细胞表面循环以驱动肝细胞癌转移。癌细胞30（3），444-458（2016）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hsu, R.-M. et al. Golgi tethering factor golgin-97 suppresses breast cancer cell invasiveness by modulating NF-κB activity. Cell Communication and Signaling 16, 1–17 (2018).Article

Hsu，R.-M.等人。高尔基体束缚因子golgin-97通过调节NF-κB活性来抑制乳腺癌细胞的侵袭性。细胞通讯和信号16,1-17（2018）。文章

Google Scholar

谷歌学者

Baschieri, F. et al. Spatial control of Cdc42 signalling by a GM130–RasGRF complex regulates polarity and tumorigenesis. Nature Communications 5(1), 4839 (2014).Article

Baschieri，F。等人。通过GM130-RasGRF复合物对Cdc42信号传导的空间控制调节极性和肿瘤发生。自然通讯5（1），4839（2014）。文章

ADS

CAS

中科院

PubMed

Google Scholar

谷歌学者

Uribe, M. L., Marrocco, I. & Yarden, Y. EGFR in cancer: Signaling mechanisms, drugs, and acquired resistance. Cancers 13(11), 2748 (2021).Article

Uribe，M.L.，Marrocco，I。＆Yarden，Y。癌症中的EGFR：信号传导机制，药物和获得性耐药。癌症13（11），2748（2021）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sharma, S. V. et al. Epidermal growth factor receptor mutations in lung cancer. Nature Reviews Cancer 7(3), 169–181 (2007).Article

Sharma，S.V.等人。肺癌中的表皮生长因子受体突变。。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Guo, Y. J. et al. ERK/MAPK signalling pathway and tumorigenesis. Experimental and therapeutic medicine 19(3), 1997–2007 (2020).PubMed

Guo，Y.J.等。ERK/MAPK信号通路与肿瘤发生。实验与治疗医学19（3），1997-2007（2020）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ullah, R., et al. RAF-MEK-ERK pathway in cancer evolution and treatment. in Seminars in cancer biology. 2022. Elsevier.Nan, X. et al. EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer. Oncotarget 8(43), 75712 (2017).Article .

Ullah，R。等人。癌症进化和治疗中的RAF-MEK-ERK途径。在癌症生物学研讨会上。2022年。爱思唯尔。Nan，X。等人。EGFR TKI作为晚期EGFR突变阳性非小细胞肺癌患者的一线治疗。。文章。

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wang, J., et al., The clathrin adaptor complex-1 and Rab12 regulate post-golgi trafficking of WT epidermal growth factor receptor (EGFR). Journal of Biological Chemistry, 2023. 299(3).Gurung, S. et al. The exosome journey: from biogenesis to uptake and intracellular signalling. Cell Communication and Signaling 19(1), 47 (2021).Article .

Wang，J。等人，网格蛋白衔接子复合物-1和Rab12调节WT表皮生长因子受体（EGFR）的高尔基体后运输。生物化学杂志，2023年。299（3）。Gurung，S.等人，《外泌体之旅：从生物发生到摄取和细胞内信号传导》。细胞通信和信号19（1），47（2021）。文章。

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hessvik, N. P. & Llorente, A. Current knowledge on exosome biogenesis and release. Cellular and Molecular Life Sciences 75(2), 193–208 (2018).Article

Hessvik，N.P。＆Llorente，A。关于外泌体生物发生和释放的最新知识。细胞与分子生命科学75（2），193-208（2018）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Paskeh, M. D. A. et al. Emerging role of exosomes in cancer progression and tumor microenvironment remodeling. Journal of Hematology & Oncology 15(1), 83 (2022).Article

。血液学与肿瘤学杂志15（1），83（2022）。文章

CAS

中科院

Google Scholar

谷歌学者

Dai, J. et al. Exosomes: key players in cancer and potential therapeutic strategy. Signal Transduction and Targeted Therapy 5(1), 145 (2020).Article

Dai，J。等人。外泌体：癌症和潜在治疗策略的关键参与者。。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Walcher, L., et al., Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies. Frontiers in Immunology, 2020. 11.Ribatti, D., Tamma, R. & Annese, T. Epithelial-mesenchymal transition in cancer: a historical overview. Translational oncology 13(6), 100773 (2020).Article .

Walcher，L。等人，《癌症干细胞起源和生物标志物：靶向个性化治疗的前景》。免疫学前沿，2020年。11.Ribatti，D.，Tamma，R。＆Annese，T。癌症中的上皮-间质转化：历史概述。转化肿瘤学13（6），100773（2020）。文章。

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kalluri, R. and V.S. LeBleu, The biology, function, and biomedical applications of exosomes. Science, 2020. 367(6478): p. eaau6977.Talukdar, S. et al. EGFR: An essential receptor tyrosine kinase-regulator of cancer stem cells. Adv Cancer Res 147, 161–188 (2020).Article

Kalluri，R.和V.S.LeBleu，外泌体的生物学，功能和生物医学应用。科学，2020年。367（6478）：p。eaau6977。Talukdar，S。等人。EGFR：癌症干细胞的必需受体酪氨酸激酶调节剂。Adv Cancer Res 147161-188（2020）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Lo, H.-W. et al. Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer research 67(19), 9066–9076 (2007).Article

Lo，H.-W.等人。表皮生长因子受体与信号转导和转录激活因子3协同作用，通过上调TWIST基因表达诱导癌细胞上皮-间质转化。癌症研究67（19），9066-9076（2007）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gautschi, O. et al. Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation. Lung cancer 55(1), 1–14 (2007).Article

Gautschi，O。等。非小细胞肺癌中的细胞周期蛋白D1：恶性转化的关键驱动因素。肺癌55（1），1-14（2007）。文章

PubMed

Google Scholar

谷歌学者

Ohashi, Y. et al. Targeting the Golgi apparatus to overcome acquired resistance of non-small cell lung cancer cells to EGFR tyrosine kinase inhibitors. Oncotarget 9(2), 1641 (2018).Article

Ohashi，Y。等人。靶向高尔基体以克服非小细胞肺癌细胞对EGFR酪氨酸激酶抑制剂的获得性抗性。Oncotarget 9（2），1641（2018）。文章

PubMed

Google Scholar

谷歌学者

Chambard, J.-C., et al., ERK implication in cell cycle regulation. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2007. 1773(8): p. 1299–1310.Maik-Rachline, G., Hacohen-Lev-Ran, A. & Seger, R. Nuclear ERK: mechanism of translocation, substrates, and role in cancer. International journal of molecular sciences 20(5), 1194 (2019).Article .

Chambard，J.-C。等人，ERK在细胞周期调控中的意义。生物化学与生物物理学报（BBA）-分子细胞研究，2007。1773（8）：第1299-1310页。Maik-Rachline，G.，Hacohen-Lev-Ran，A。＆Seger，R。核ERK：易位机制，底物和在癌症中的作用。国际分子科学杂志20（5），1194（2019）。文章。

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wolf, I. et al. Involvement of the activation loop of ERK in the detachment from cytosolic anchoring. Journal of Biological Chemistry 276(27), 24490–24497 (2001).Article

Wolf，I.等人，《ERK激活环参与胞质锚定的分离》，《生物化学杂志》276（27），24490–24497（2001）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Plotnikov, A., et al., Nuclear extracellular signal-regulated kinase 1 and 2 translocation is mediated by casein kinase 2 and accelerated by autophosphorylation. Molecular and cellular biology, 2011.Hume, S., Dianov, G. L. & Ramadan, K. A unified model for the G1/S cell cycle transition.

Plotnikov，A。等人，核细胞外信号调节激酶1和2易位由酪蛋白激酶2介导，并通过自磷酸化加速。分子与细胞生物学，2011。Hume，S.，Dianov，G.L。和Ramadan，K。G1/S细胞周期转变的统一模型。

Nucleic acids research 48(22), 12483–12501 (2020).Article .

核酸研究48（22），12483-12501（2020）。文章。

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sobecki, M. et al. Cell-cycle regulation accounts for variability in Ki-67 expression levels. Cancer research 77(10), 2722–2734 (2017).Article

Sobecki，M。等人。细胞周期调控解释了Ki-67表达水平的变异性。癌症研究77（10），2722-2734（2017）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Uxa, S. et al. Ki-67 gene expression. Cell Death & Differentiation 28(12), 3357–3370 (2021).Article

Uxa，S。等人Ki-67基因表达。细胞死亡与分化28（12），3357-3370（2021）。文章

CAS

中科院

Google Scholar

谷歌学者

Farber-Katz, S. E. et al. DNA damage triggers Golgi dispersal via DNA-PK and GOLPH3. Cell 156(3), 413–427 (2014).Article

DNA损伤通过DNA-PK和GOLPH3触发高尔基体扩散。细胞156（3），413-427（2014）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chang, S.-H. et al. GOLGA2/GM130, cis-Golgi matrix protein, is a novel target of anticancer gene therapy. Molecular Therapy 20(11), 2052–2063 (2012).Article

Chang，S.-H.等人。GOLGA2/GM130，顺式高尔基体基质蛋白，是抗癌基因治疗的新靶点。分子疗法20（11），2052-2063（2012）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Song, Q. et al. The functional landscape of Golgi membrane protein 1 (GOLM1) phosphoproteome reveal GOLM1 regulating P53 that promotes malignancy. Cell death discovery 7(1), 42 (2021).Article

Song，Q。等人。高尔基体膜蛋白1（GOLM1）磷酸化蛋白质组的功能景观揭示了GOLM1调节P53促进恶性肿瘤。细胞死亡发现7（1），42（2021）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Li, L. M. Overexpression of golgi membrane protein 1 promotes non-small-cell carcinoma aggressiveness by regulating the matrix metallopeptidase 13. American journal of cancer research 8(3), 551 (2018).MathSciNet

Li，L.M。高尔基体膜蛋白1的过表达通过调节基质金属肽酶13促进非小细胞癌的侵袭性。美国癌症研究杂志8（3），551（2018）。数学网

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sigismund, S., Avanzato, D. & Lanzetti, L. Emerging functions of the EGFR in cancer. Molecular oncology 12(1), 3–20 (2018).Article

Sigismund，S.，Avanzato，D。＆Lanzetti，L。EGFR在癌症中的新兴功能。分子肿瘤学12（1），3-20（2018）。文章

PubMed

Google Scholar

谷歌学者

Maisel, S.A. and J. Schroeder, Wrong place at the wrong time: how retrograde trafficking drives cancer metastasis through receptor mislocalization. J. Cancer Metastasis Treat, 2019. 5(7).Olea-Flores, M. et al. Extracellular-signal regulated kinase: a central molecule driving epithelial–mesenchymal transition in cancer.

Maisel，S.A.和J.Schroeder，《错误时间的错误地点：逆行运输如何通过受体错位驱动癌症转移》。J、癌症转移治疗，2019年。5（7）。Olea Flores，M。等。细胞外信号调节激酶：驱动癌症上皮-间质转化的中心分子。

International journal of molecular sciences 20(12), 2885 (2019).Article .

国际分子科学杂志20（12），2885（2019）。文章。

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sun, Z. et al. Effect of exosomal miRNA on cancer biology and clinical applications. Molecular cancer 17, 1–19 (2018).Article

Sun，Z.等人。外泌体miRNA对癌症生物学和临床应用的影响。分子癌症17,1-19（2018）。文章

Google Scholar

谷歌学者

Kim, O. et al. Syntenin-1-mediated small extracellular vesicles promotes cell growth, migration, and angiogenesis by increasing onco-miRNAs secretion in lung cancer cells. Cell Death & Disease 13(2), 122 (2022).Article

Kim，O。等人。Syntenin-1介导的小细胞外囊泡通过增加肺癌细胞中癌miRNA的分泌来促进细胞生长，迁移和血管生成。细胞死亡与疾病13（2），122（2022）。文章

CAS

中科院

Google Scholar

谷歌学者

Blanc, L. & Vidal, M. New insights into the function of Rab GTPases in the context of exosomal secretion. Small GTPases 9(1–2), 95–106 (2018).Article

Blanc，L。＆Vidal，M。在外泌体分泌的背景下对Rab GTPases功能的新见解。小GTPases 9（1-2），95-106（2018）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Ostrowski, M. et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nature Cell Biology 12(1), 19–30 (2010).Article

。自然细胞生物学12（1），19-30（2010）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Hayes, G. L. et al. Multiple Rab GTPase binding sites in GCC185 suggest a model for vesicle tethering at the trans-Golgi. Molecular biology of the cell 20(1), 209–217 (2009).Article

。细胞的分子生物学20（1），209-217（2009）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Liu, P. et al. Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancer. Journal of translational medicine 21(1), 40 (2023).Article

Liu，P。等人。血浆外泌体蛋白和代谢产物的改变与去势抵抗性前列腺癌的进展有关。转化医学杂志21（1），40（2023）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wang, C. et al. Exosomes carrying ALDOA and ALDH3A1 from irradiated lung cancer cells enhance migration and invasion of recipients by accelerating glycolysis. Molecular and cellular biochemistry 469, 77–87 (2020).Article

Wang，C.等人。携带来自受照射肺癌细胞的ALDOA和ALDH3A1的外泌体通过加速糖酵解来增强受体的迁移和侵袭。分子和细胞生物化学469,77-87（2020）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Download referencesAcknowledgementsThis work was supported by the Ministry of Science and ICT (2019M3E5D5065399), the National Research Foundation of Korea (NRF-2020R1A2C1101294), and the Ministry of Health and Welfare (RS-2022-00060247) of the government of the Republic of Korea.FundingMinistry of Science and ICT, South Korea, 2019M3E5D5065399; National Research Foundation of Korea, NRF-2020R1A2C1101294; Ministry of Health and Welfare, South Korea, RS-2022-00060247.Author informationAuthor notesMin Sang Kim and Hyesun Jeong contributed equally.Authors and AffiliationsDepartment of Integrated Biomedical and Life Science, Graduate School of Korea University, Seoul, 02855, Republic of KoreaMin Sang Kim, Jiho Park, Gun Seop Shin & Sunghoi HongBK21 FOUR R&E Center for Precision Public Health, Graduate School of Korea University, Seoul, 02855, Republic of KoreaMin Sang Kim, Jiho Park, Gun Seop Shin, Yeonho Choi & Sunghoi HongSchool of Biosystems and Biomedical Sciences, Korea University, Seoul, 02841, Republic of KoreaHyesun Jeong & Sunghoi HongDepartment of Thoracic and Cardiovascular Surgery, College of Medicine, Korea University Guro Hospital, Seoul, 08308, Republic of KoreaByeong Hyeon Choi, Ok Hwa Jeon & Hyun Koo KimImage Guided Precision Cancer Surgery Institute, Korea University, Seoul, 02841, KoreaByeong Hyeon Choi, Ok Hwa Jeon & Hyun Koo KimDepartment of Bio and Brain Engineeringand, KAIST Institute for Health Science and Technology, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of KoreaJik-Han Jung & Ji-Ho ParkEXoPERT Corporation, Seoul, 02580, Republic of KoreaHyunku Shin, Jewon Yu & Yeonho ChoiDivision of Hematology-Oncology, Department of Internal Medicine, Korea University College of Medicine, Seoul, 02841, Republi.

。资助韩国科学与信息通信技术部，2019M3E5D5065399；韩国国家研究基金会，NRF-2020R1A2C1101294；韩国卫生福利部，RS-2022-00060247。作者信息作者notesMin Sang Kim和Hyesun Jeong贡献相同。作者和附属机构韩国大学研究生院综合生物医学与生命科学系，首尔，02855，大韩民国生金，Jiho Park，Gun Seop Shin＆Sunghoi HongBK21韩国大学研究生院精密公共卫生四R＆E中心，首尔，02855，大韩民国生金，Jiho Park，Gun Seop Shin，Yeonho Choi＆Sunghoi Hong韩国大学生物系统与生物医学科学学院，首尔，02841，大韩民国全正和Sunghoi Hong韩国大学医学院胸心血管外科，首尔古罗医院，08308，KoreaByeong Hyeon Choi共和国，Ok Hwa Jeon＆Hyun Koo Kim韩国大学图像引导精准癌症外科研究所，首尔，02841，KoreaByeong Hyeon Choi，Ok Hwa Jeon＆Hyun Koo Kim生物与脑工程系韩国大田高等科学技术研究所KAIST健康科学与技术研究所，34141，大韩民国韩正和纪浩帕克斯珀特公司，首尔，02580，大韩民国韩国信，Jewon Yu和Yeonho Choi大韩民国大学医学院内科血液肿瘤科，首尔，02841，共和国。

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PubMed Google ScholarContributionsConception and design: M.S.K., H.J., S.H.; acquisition, analysis, and interpretation of data: M.S.K., H.J., J.P., G.S.S., S.H.; manuscript preparation: M.S.K., H.J., S.H.; review and editing: M.S.K., H.J., B.H.C., J.P., G.S.S., J.-H.J., H.S, K.-W.K., O.H.J., J.Y., J.-H.P., Y.P., Y.C., H.K.K., S.H.; funding and final manuscript approval: S.H.

PubMed谷歌学术贡献概念与设计：M.S.K.，H.J.，S.H。；数据的获取，分析和解释：M.S.K.，H.J.，J.P.，G.S.S.，S.H。；手稿准备：M.S.K.，H.J.，S.H。；审查和编辑：M.S.K.，H.J.，B.H.C.，J.P.，G.S.S.，J.-H.J.，H.S，K.-W.K.，O.H.J.，J.Y.，J.-H.P.，Y.P.，Y.C.，H.K.K.，S.H。；资金和最终稿件批准：S.H。

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Reprints and permissionsAbout this articleCite this articleKim, M.S., Jeong, H., Choi, B.H. et al. GCC2 promotes non-small cell lung cancer progression by maintaining Golgi apparatus integrity and stimulating EGFR signaling pathways.

转载和许可本文引用本文Kim，M.S.，Jeong，H.，Choi，B.H。等人。GCC2通过维持高尔基体的完整性和刺激EGFR信号通路来促进非小细胞肺癌的进展。

Sci Rep 14, 28926 (2024). https://doi.org/10.1038/s41598-024-75316-1Download citationReceived: 21 February 2024Accepted: 04 October 2024Published: 22 November 2024DOI: https://doi.org/10.1038/s41598-024-75316-1Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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KeywordsGRIP and coiled-coil domain containing 2 (GCC2)Non-small cell lung cancer (NSCLC)ExosomesCancer growth signalingGolgi apparatus

关键词RIP和卷曲螺旋结构域包含2（GCC2）非小细胞肺癌（NSCLC）外泌体扫描生长信号高尔基体

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