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Expression of α-catenin in α-catenin-deficient cells results in a reduced proliferation in three-dimensional multicellular spheroids but not in two-dimensional monolayer cultures

Oncogene volume 23, pages 2694–2702 (2004)Cite this article

Abstract

α-Catenin is an intracellular protein that associates with the carboxy-terminal region of cadherin, a cell adhesion molecule, via β-catenin or γ-catenin (plakoglobin). Linkage of cadherin to the cytoskeleton by catenins is required for full cadherin activity. Following transfection of an α-catenin-deficient colon carcinoma cell line with a series of α-catenin constructs, we discovered that the restoration of α-catenin expression results in reduced proliferation in three-dimensional multicellular spheroids, but not in two-dimensional monolayer cultures. The cellular function of α-catenin has not been compared between cells in three- and two-dimensional culture; this is the first evidence that growth regulation in three-dimensional cultures requires signaling mediated by α-catenin. Two classes of constructs, containing deletions in either the central segment or the COOH terminus of the molecule, both induced morphological changes, including cell compaction, and suppressed cell growth in three-dimensional cultures. In α-catenin-expressing cells, inhibition of cadherin cell adhesion by treatment with anti-E-cadherin antibodies resulted in a similar phenotype as that observed following the loss of α-catenin. Therefore, both the homophilic interaction of the cadherin extracellular domain and the linkage of the cadherin cytoplasmic domain to the actin cytoskeleton by α-catenin are necessary for growth control in three-dimensional culture.

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Acknowledgements

We are grateful to Tamotsu Taniguchi for his help with these experiments and to Kumiko Sato for her administrative assistance. This work was supported by a Grant-in-Aid for Science Research on Priority Areas from the Ministry of Education, Science and Culture of Japan (B).

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  1. Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Science, Kagoshima University, Kagoshima, 890-8544, Japan

    Shyuichiro Matsubara & Masayuki Ozawa

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  1. Shyuichiro Matsubara
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  2. Masayuki Ozawa
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Correspondence to Shyuichiro Matsubara.

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Matsubara, S., Ozawa, M. Expression of α-catenin in α-catenin-deficient cells results in a reduced proliferation in three-dimensional multicellular spheroids but not in two-dimensional monolayer cultures. Oncogene 23, 2694–2702 (2004). https://doi.org/10.1038/sj.onc.1207423

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