4.5 Article

Regulation of CD44 expression and focal adhesion by Golgi phosphatidylinositol 4-phosphate in breast cancer

Journal

CANCER SCIENCE
Volume 107, Issue 7, Pages 981-990

Publisher

WILEY
DOI: 10.1111/cas.12968

Keywords

Breast cancer; CD44; focal adhesion; phosphatidylinositol-4-monophosphate; SAC1

Categories

Funding

  1. Japan Society for the Promotion of Science [25130707, 25460365]
  2. Hyogo Science and Technology Association
  3. Ministry of Education, Culture, Sports, Science and Technology of Japan [23227005]
  4. Grants-in-Aid for Scientific Research [25460365, 15K14381, 16K08585, 23227005] Funding Source: KAKEN

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CD44, a transmembrane receptor, is expressed in the standard or variant form and plays a critical role in tumor progression and metastasis. This protein regulates cell adhesion and migration in breast cancer cells. We previously reported that phosphatidylinositol-4-phosphate (PI(4)P) at the Golgi regulates cell migration and invasion in breast cancer cell lines. In this study, we showed that an increase in PI(4) P levels at the Golgi by knockdown of PI(4) P phosphatase SAC1 increased the expression of standard CD44, variant CD44, and ezrin/radixin phosphorylation and enhanced the formation of focal adhesions mediated by CD44 and ezrin/radixin in MCF7 and SK-BR-3 cells. In contrast, knockdown of PI 4-kinase IIIb in highly invasive MDA-MB-231 cells decreased these factors. These results suggest that SAC1 expression and PI(4) P at the Golgi are important in tumor progression and metastasis and are potential prognostic markers of breast cancers.

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