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Knockdown of the α5 laminin chain affects differentiation of colorectal cancer cells and their sensitivity to chemotherapy.
Biochimie ( IF 3.3 ) Pub Date : 2020-04-22 , DOI: 10.1016/j.biochi.2020.04.016
Diana Maltseva 1 , Maria Raygorodskaya 2 , Evgeny Knyazev 3 , Victor Zgoda 4 , Olga Tikhonova 4 , Shan Zaidi 5 , Sergey Nikulin 6 , Ancha Baranova 7 , Andrey Turchinovich 8 , Sergey Rodin 9 , Alexander Tonevitsky 1
Affiliation  

The interaction of tumor cells with the extracellular matrix (ECM) may affect the rate of cancer progression and metastasis. One of the major components of ECM are laminins, the heterotrimeric glycoproteins consisting of α-, β-, and γ-chains (αβγ). Laminins interact with their cell surface receptors and, thus, regulate multiple cellular processes. In this work, we demonstrate that shRNA-mediated knockdown of the α5 laminin chain results in Wnt- and mTORC1-dependent partial dedifferentiation of colorectal cancer cells. Furthermore, we showed that this dedifferentiation involved activation of ER-stress signaling, pathway promoting the sensitivity of cells to 5-fluorouracil.

中文翻译:

敲低α5层粘连蛋白链影响大肠癌细胞的分化及其对化疗的敏感性。

肿瘤细胞与细胞外基质(ECM)的相互作用可能会影响癌症进展和转移的速度。ECM的主要成分之一是层粘连蛋白,即由α-,β-和γ-链(αβγ)组成的异三聚体糖蛋白。层粘连蛋白与其细胞表面受体相互作用,从而调节多个细胞过程。在这项工作中,我们证明了shRNA介导的α5层粘连蛋白链的敲低导致大肠癌细胞Wnt和mTORC1依赖性部分去分化。此外,我们表明,这种去分化涉及内质网应激信号的激活,促进细胞对5-氟尿嘧啶敏感性的途径。
更新日期:2020-04-22
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