Effect of CD44 on glioma cell progression, invasion and senescence

• Glioblastoma multiforme (GBM) is a lethal brain tumor, characterized by enhanced proliferation rate, increased invasive capacity, and chemoresistance. The expression of the hyaluronan receptor CD44 correlates with GBM progression and poor prognosis. We have initiated studies to elucidate the molecular mechanisms behind the effects of CD44 on tumorigenesis by knocking out (KO) CD44, via employing CRISPR/Cas9 gene editing in U251MG cells. CD44-depleted cells exhibited impaired proliferation rate, as confirmed by decreased cell numbers, Ki67 positive nuclei, diminished p-CREB levels, and increased levels of the cell cycle inhibitor p16 compared to control cells. Furthermore, the CD44 KO cells acquired a pro-senescence state, which was manifested upon serum deprivation. Interestingly, CD44 KO cells showed enhanced migratory and invasive properties, as observed in 2D wound healing and 3D collagen assays, which may be partially attributed to the acquisition of a senescence-associated secretory phenotype (SASP) and activation of the ERK1/2 MAPK pathway. RNA-sequencing analysis of stem-like U251MG cells, grown in spheres, unveiled a CD44-dependency for expression of molecules involved in hyaluronan synthesis and degradation, and of members of the PDGF and PDGF receptor families. These observations highlight the importance of CD44 on GBM progression. 

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MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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