崔永萍課題組報(bào)道食管鱗癌中FAT1調(diào)控細(xì)胞的干性和順鉑耐藥性
2022年5月23日山西醫(yī)科大學(xué)轉(zhuǎn)化醫(yī)學(xué)研究中心崔永萍課題組在Molecular and Cellular Biochemistry雜志上發(fā)表題為“FAT1 downregulation enhances stemness and cisplatin resistance in esophageal squamous cell carcinoma”的論文,該研究探討突變基因FAT1對食管鱗癌細(xì)胞的干性和順鉑耐藥性的影響,為食管鱗癌患者治療過程中化療耐藥的逆轉(zhuǎn)提供了新的思路和靶點(diǎn)。
食管鱗癌患者由于缺乏早期特異性癥狀和有效檢測手段,首次就診時(shí)多處于中晚期,五年生存率不到30%。治療手段主要包括手術(shù)結(jié)合放化療?;熯^程中產(chǎn)生的藥物耐藥是導(dǎo)致化療失敗的主要原因,順鉑是食管鱗癌患者的常用化療藥物,順鉑耐藥是導(dǎo)致化療失敗的重要因素,因此明確導(dǎo)致順鉑耐藥的分子機(jī)制尤為重要。
圖1.FAT1與食管鱗癌細(xì)胞干性的相關(guān)性
圖2.FAT1調(diào)控食管鱗癌細(xì)胞的克隆和增殖能力
圖3.FAT1調(diào)控食管鱗癌細(xì)胞對順鉑的耐藥性
該研究通過探討FAT1對食管鱗癌細(xì)胞干性和順鉑耐藥性的調(diào)控及其發(fā)揮作用的分子機(jī)制,明確了FAT1通過Wnt/β-catenin信號通路調(diào)控ABCC3進(jìn)而調(diào)控食管鱗癌細(xì)胞的干性和耐藥性,為食管鱗癌患者順鉑耐藥性的逆轉(zhuǎn)提供了新的治療思路和靶點(diǎn)。
參考文獻(xiàn):
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A(2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492
2. Arnold M, Soerjomataram I, Ferlay J, Forman D (2015) Global incidence of oesophageal cancer by histological subtype in 2012.Gut 64:381–387. https://doi.org/10.1136/gutjnl-2014-308124
3. Wang T, Yu J, Liu M, Chen Y, Zhu C, Lu L, Wang M, Min L,Liu X, Zhang X, Gubat JA, Chen Y (2019) The beneft of taxanebased therapies over fuoropyrimidine plus platinum (FP) in the treatment of esophageal cancer: a meta-analysis of clinical studies.
Drug Des Dev Ther 13:539–553. https://doi.org/10.2147/DDDT.S189514
4. Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, Nakamura T, Yabusaki H, Aoyama N, Kurita A, Ikeda K, Kanda T,Tsujinaka T, Nakamura K, Fukuda H (2012) A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fuorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol 19:68–74. https://doi.org/10.1245/s10434-011-2049-9
5. Ter Veer E, Haj Mohammad N, van Valkenhoef G, Ngai LL,Mali RMA, Anderegg MC, van Oijen MGH, van Laarhoven HWM (2016) The efcacy and safety of frst-line chemotherapy in advanced esophagogastric cancer: a network meta-analysis. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djw166
6. Ilson DH (2008) Esophageal cancer chemotherapy: recent advances. Gastrointest Cancer Res 2:85–92
7. Altorki N, Harrison S (2017) What is the role of neoadjuvant chemotherapy, radiation, and adjuvant treatment in resectable esophageal cancer? Ann Cardiothorac Surg 6:167–174. https://doi.org/10.21037/acs.2017.03.16
8. Shibue T, Weinberg RA (2017) EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol14:611–629. https://doi.org/10.1038/nrclinonc.2017.44
9. Farmer P, Bonnefoi H, Anderle P, Cameron D, Wirapati P, BecetteV, Andre S, Piccart M, Campone M, Brain E, Macgrogan G, Petit T, Jassem J, Bibeau F, Blot E, Bogaerts J, Aguet M, Bergh J, Iggo R, Delorenzi M (2009) A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med 15:68–74. https://doi.org/10.1038/nm.1908
10. Scheel C, Eaton EN, Li SH, Chafer CL, Reinhardt F, Kah KJ, Bell G, Guo W, Rubin J, Richardson AL, Weinberg RA (2011) Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell 145:926–940. https://doi.
org/10.1016/j.cell.2011.04.029
11. Ni T, Li XY, Lu N, An T, Liu ZP, Fu R, Lv WC, Zhang YW, Xu XJ, Grant Rowe R, Lin YS, Scherer A, Feinberg T, Zheng XQ, Chen BA, Liu XS, Guo QL, Wu ZQ, Weiss SJ (2016) Snail1-dependent p53 repression regulates expansion and activity of
tumour-initiating cells in breast cancer. Nat Cell Biol 18:1221–1232. https://doi.org/10.1038/ncb3425