Rac1 as a multifunctional therapeutic target to prevent and combat cancer metastasis

Abstract

ABSTRACT:Metastatic

Radiation resistance: Cancer stem cells (CSCs) and their enigmatic pro-survival signaling

“…[64]. Previously dormant cells give rise to an increased number of CSCs in cell culture [31] (Fig. 2A).…”

“…Some of them are closely related to bioenergetic stress and cancer cell metabolism (CD133, ALDH1) [26][27][28], and others are expressed to differing degrees at different stages of the cell cycle [29,30]. Despite such limitations, it has been shown that carcinoma cells overexpress CD133, CD44, ALDH1, Bmi-1 and other currently known CSC markers, and that they are resistant to ionizing radiation and chemotherapeutic drugs [28,29,31,32]. Most reports on the molecular patterns of CSCs are based on findings in carcinoma cells positive for any of the above CSC markers.…”

“…In carcinoma cell lines with acquired radioresistance and CSC enrichment, all classes of ROS scavengers are up-regulated [12,14,31,[49][50][51]. Recent preclinical studies have shown that the enhanced expression of ROS scavengers protects CSCs from ionizing radiation and that the oxygenation status of the malignant tumors does not play a significant role in this CSC radiation resistance [52].…”

“…A number of reports indicate that CSCs proliferate more slowly than non-stem carcinoma cells [12,21,31,50,61,62]. Gao et al demonstrated that ovarian cancer cells possessing tumorigenic abilities and expressing CSC markers (CD24, nestin, oct4, Notch1 and Notch4) proliferated more slowly than the bulk tumor cells [62].…”

“…Furthermore, up-regulation of the CSC specific marker CD44 variant 8-10 and of c-myc is a sign of metastatically active and proliferating CSCs, whereas high expression of the CD44 variant 8-10 accompanied by down-regulation of c-myc characterizes dormant CSCs [15,68]. Our research group has recently shown that slowly proliferating radiation resistant prostate, breast and head and neck carcinoma cells contain a higher proportion of cells with the CSC phenotype CD44+/CD24−/ALDH1+, up-regulation of Notch-1 and concomitant down-regulation of PTEN [31]. Despite the pronounced interest of researchers in the role of cancer cell dormancy and its relationship to treatment resistance followed by recurrence, the molecular properties of the quiescent or dormant cells are still poorly investigated.…”