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Elucidation of molecular and functional heterogeneity through differential
expression network analyses of discrete tumor subsets
#MMPMID27140846
Naik RR
; Gardi NL
; Bapat SA
Sci Rep
2016[May]; 6
(?): 25261
PMID27140846
show ga
Intratumor heterogeneity presents a major hurdle in cancer therapy. Most current
research studies consider tumors as single entities and overlook molecular
diversity between heterogeneous state(s) of different cells assumed to be
homogenous. The present approach was designed for fluorescence-activated cell
sorting-based resolution of heterogeneity arising from cancer stem cell (CSC)
hierarchies and genetic instability in ovarian tumors, followed by
microarray-based expression profiling of sorted fractions. Through weighted gene
correlation network analyses, we could assign enriched modules of co-regulated
genes to each fraction. Such gene modules often correlate with biological
functions; one such specific association was the enrichment of CD53 expression in
CSCs, functional validation indicated CD53 to be a tumor-initiating cell- rather
than quiescent CSC-marker. Another association defined a state of poise for
stress-induced metastases in aneuploid cells. Our results thus emphasize the need
for studying cell-specific functionalities relevant to regeneration, drug
resistance and disease progression in discrete tumor cell fractions.
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