4.3 Article

Sox2 modulates motility and enhances progression of colorectal cancer via the Rho-ROCK signaling pathway

Journal

ONCOTARGET
Volume 8, Issue 58, Pages 98635-98645

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.21709

Keywords

Sox2; colorectal cancer; cancer stem cell; motility; ROCK

Funding

  1. National Natural Science Foundation of China [31371390]
  2. Doctoral Program of Ministry of Education of the People's Republic of China [20130171110010]
  3. Guangdong Provicial Key Scientific and Technological Projects on Technology Development and Industrialization [2016B030231001]

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Sox2 (Sry-box2) is essential for a variety of stem cells and is also expressed in colorectal cancer (CRC). However, the underlying mechanism by which Sox2 enhances CRC progression remains unclear. In the present study, we show that elevated Sox2 expression is significantly correlated with poor clinical prognosis. CRC is phenotypically heterogeneous, and harbors several subtypes of cancer cells. Elevated Sox2 expression was always detected in rounded-shape cells, which co-located to poorly differentiated regions, the invasive frontier and metastatic lesions. Knockdown of Sox2 in CRC cells not only decreased the number of round-shaped cells, but also suppressed cell migration, invasion as well as attenuated colony forming capacity and tumorigenicity. By contrast, overexpression of Sox2 in CRC cells was associated with up-regulation of multidrug resistance genes and accelerated CRC progression. Moreover, Sox2 conferred activation of Rho-ROCK signaling, whereas inhibition of ROCK signaling decreased cell migration, invasion, colony formation and self-renewal of CRC. Our results reveal that CRC is phenotypically and functionally heterogeneous. Elevated Sox2 expression activates the Rho-ROCK pathway, which in turn changes cell morphology and promotes cell migration and progression.

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