Knockdown of the α5 laminin chain affects differentiation of colorectal cancer cells and their sensitivity to chemotherapy

Diana Maltseva, Maria Raygorodskaya, Evgeny Knyazev, Victor Zgoda, Olga Tikhonova, Shan Zaidi, Sergey Nikulin, Ancha Baranova, Andrey Turchinovich, Sergey Rodin, Alexander Tonevitsky

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)107-116
Number of pages10
JournalBiochimie
Volume174
DOIs
StatePublished - Jul 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)

Funding

The study was supported by the Russian Science Foundation (project 17-14-01338 ).

FundersFunder number
Russian Science Foundation17-14-01338

    Keywords

    • Colorectal cancer
    • Dedifferentiation
    • HT29
    • Intestinal epithelium stem cell marker
    • LAMA5
    • Laminin

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