CD44 is an adhesion molecule expressed in cancer stem-like cells. Here, we show that a CD44 variant (CD44v) interacts with xCT, a glutamate-cystine transporter, and controls the intracellular level of reduced glutathione (GSH). Human gastrointestinal cancer cells with a high level of CD44 expression showed an enhanced capacity for GSH synthesis and defense against reactive oxygen species (ROS). Ablation of CD44 induced loss of xCT from the cell surface and suppressed tumor growth in a transgenic mouse model of gastric cancer. It also induced activation of p38(MAPK), a downstream target of ROS, and expression of the gene for the cell cycle inhibitor p21(CIP1/WAF1). These findings establish a function for CD44v in regulation of ROS defense and tumor growth.

Takamura et al. show that most lung CD8+ TRM cells are not maintained in the inducible bronchus-associated lymphoid tissue (iBALT) but are maintained in specific niches created at the site of tissue regeneration, which are termed as repair-associated memory depots (RAMDs).

Human RECQL1 and RECQL5 belong to the RecQ family that includes Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome causative genes. Cells derived from individuals suffering from these syndromes show significant levels of genomic instability. However, neither RECQL1 nor RECQL5 has been related to a disease, and nothing is known about the functions of RecQL1 and RecQL5. We generated here The Escherichia coli RecQ helicase is one of the proteins involved in the recF recombination pathway that is effective in the recBCD sbcB background (23). In human cells, five genes encoding RecQ helicase homologues have been identified, and three are the causative genes for Bloom syndrome (BS), Werner syndrome (WS), and Rothmund-Thomson syndrome (RTS) (4, 17, 40). The remaining two are RECQL1 and RECQL5 (16,26,27). BS is a rare genetic disorder characterized by retarded growth, sunlight sensitivity, immunodeficiency, male infertility, and predisposition to a wide variety of malignant tumors. The most characteristic feature of BS cells is genomic instability, which is manifested as an elevated frequency of chromosome breaks, interchange between homologous chromosomes, and sister chromatid exchange (SCE) (10). The other two genetic disorders, WS and RTS, also show genomic instability (21).Before we cloned a cDNA encoding RecQL1, we purified this protein and designated it DNA-dependent ATPase Q1 and later DNA helicase Q1 because of its DNA helicase activity (28, 39). Puranam and Blackshear named the gene encoding this protein RECQL (26). Due to these circumstances and the existence of multiple RecQ homologues in higher eukaryotic cells, we propose to designate this gene RECQL1 (5). Although RecQL1 is a major DNA helicase in human cells, the function of this helicase is not known at all (28).The fourth and fifth RECQ homologues, originally called RecQ4 and RecQ5 and recently called RECQL4 and RECQL5 (5, 17), were cloned in 1998 after a search for sequences similar to the RecQ helicase motifs in the expressed sequence tag database (16). Mutations in the RECQL4 gene have been found in patients with RTS, a rare genetic disorder characterized by premature aging and a predisposition to cancers such as those typical of WS (17). At present, no genetic disorder has been identified that is caused by mutations in the RECQL1 or RECQL5 gene. This circumstance suggests that RecQL1 and RecQL5 are indispensable for cell viability.In contrast to human cells, a unicellular eukaryote, Saccharomyces cerevisiae, has a sole gene that encodes a RecQ helicase homologue, SGS1 (slow growth suppressor 1). The sgs1 mutants show multiple phenotypes, such as sensitivity to methyl methanesulfonate (MMS) and hydroxyurea, chromosome missegregation, poor sporulation, premature aging, and checkpoint defects (6,8,22,30,36,37). In addition, sgs1 mutants show phenotypes of mitotic hyper-recombination, including interchromosomal homologous recombination, intrachromosomal excision recombination, illegitimate recombination, and unequal sister chromatid recombin...

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