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

doi:10.1016/j.biochi.2020.04.016

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

Biochimie. 2020 Jul:174:107-116. doi: 10.1016/j.biochi.2020.04.016. Epub 2020 Apr 22.

Authors

Affiliations

¹ Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Myasnitskaya str. 13/4, 117997, Moscow, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Miklukho-Maklaya str. 16/10, 117997, Moscow, Russia; Scientific Research Center Bioclinicum, Ugreshskaya str. 2/85, 115088, Moscow, Russia. Electronic address: [email protected].
² Scientific Research Center Bioclinicum, Ugreshskaya str. 2/85, 115088, Moscow, Russia.
³ Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Myasnitskaya str. 13/4, 117997, Moscow, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Miklukho-Maklaya str. 16/10, 117997, Moscow, Russia.
⁴ Institute of Biomedical Chemistry, Pogodinskaya str. 10, 119121, Moscow, Russia.
⁵ School of Systems Biology, George Mason University, Fairfax, VA, 22030, USA.
⁶ Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Myasnitskaya str. 13/4, 117997, Moscow, Russia; Moscow Institute of Physics and Technology, Institutskiy per. 9, 141700, Dolgoprudny, Russia.
⁷ School of Systems Biology, George Mason University, Fairfax, VA, 22030, USA; Moscow Institute of Physics and Technology, Institutskiy per. 9, 141700, Dolgoprudny, Russia; Research Center of Medical Genetics, Moskvorechye str. 1, 115522, Moscow, Russia.
⁸ SciBerg e.Kfm, Birkenauer str. 7, 68309, Mannheim, Germany.
⁹ Department of Surgical Sciences, Ångström Laboratory, Uppsala University, 752 37, Uppsala, Sweden.
¹⁰ Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Myasnitskaya str. 13/4, 117997, Moscow, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Miklukho-Maklaya str. 16/10, 117997, Moscow, Russia; Scientific Research Center Bioclinicum, Ugreshskaya str. 2/85, 115088, Moscow, Russia. Electronic address: [email protected].

PMID: 32334043
DOI: 10.1016/j.biochi.2020.04.016

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.

Keywords: Colorectal cancer; Dedifferentiation; HT29; Intestinal epithelium stem cell marker; LAMA5; Laminin.

MeSH terms

Antimetabolites, Antineoplastic / pharmacology
Cell Dedifferentiation*
Colorectal Neoplasms / drug therapy
Colorectal Neoplasms / pathology*
Fluorouracil / pharmacology
Gene Knockdown Techniques
HT29 Cells
Humans
Laminin / genetics
Laminin / physiology*

Substances

Antimetabolites, Antineoplastic
Laminin
laminin alpha5
Fluorouracil