DLIC 1 , but not DLIC 2 , is upregulated in colon cancer and this contributes to proliferative overgrowth and migratory characteristics of cancer cells

• Published in: The FEBS journal Vol. 286; no. 4; pp. 803 - 820
• Main Authors: Even, Ipek, Reidenbach, Sonja, Schlechter, Tanja, Berns, Nicola, Herold, Rosanna, Roth, Wilfried, Krunic, Damir, Riechmann, Veit, Hofmann, Ilse
• Format: Journal Article
• Language: English
• Published: 01-02-2019
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.14755

Cytoplasmic dynein‐1 is a large minus‐end‐directed microtubule motor complex involved in membrane trafficking, organelle positioning, and microtubule organization. The roles of dynein light intermediate chains (
DLIC
s;
DLIC
1 and
DLIC
2) within the complex are, however, still largely undefined. In this study, we investigated the possible roles of
DLIC
s in epithelial homeostasis and colon cancer development. Mutant clonal analysis of
Drosophila
Dlic in the follicular epithelium of
Drosophila
ovary showed defects in nuclear positioning, epithelial integrity, and apical cell polarity. Consistently, knockdown of human
DLIC
1 and
DLIC
2 in colon carcinoma cells resulted in damaged epithelial organization, disturbed lumen formation, and impaired apical polarity establishment in three‐dimensional cell culture. Depletion of
DLIC
1 and
DLIC
2 led to reduced proliferation, enhanced apoptosis rates, disrupted mitotic spindle assembly, and induction of G2/M arrest in cell cycle progression. Moreover, reduced levels of
DLIC
1 in contrast to
DLIC
2 impaired the migratory ability. On the other hand, immunohistochemical examination of human colorectal tissue samples and further colorectal cancer dataset analysis showed a significant upregulation for
DLIC
1 in tumors, whereas
DLIC
2 expression was unchanged. In addition, the overexpression of
DLIC
1 caused increased proliferation, decreased apoptosis and enhanced migration, whereas
DLIC
2 overexpression did not result in any significant changes. Together, these results indicate that
DLIC
1 and
DLIC
2 contribute to the establishment and maintenance of epithelial homeostasis. Furthermore, these findings present the first evidence that
DLIC
1 and
DLIC
2 have distinct roles in colon cancer development and that
DLIC
1 may contribute to proliferative overgrowth and migratory characteristics.