CD98hc (SLC3A2) regulation of skin homeostasis wanes with age

Boulter, Etienne; Estrach, Soline; Errante, Aurélia; Pons, Catherine; Cailleteau, Laurence; Tissot, Floriane S.; Meneguzzi, Guerríno; Feral, Chloé C.

doi:10.1083/jcb2002oia5

Cited by 18 publications

(29 citation statements)

References 65 publications

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“…In contrast, crosslinking of CD99 abrogated the increased amino acid influx induced by CD98hc. This result is consistent with the previous report showing that CD98hc-dependent amino acid transport may be involved in modulating CD98-integrin-FAK-RhoA signaling pathway [21]. Taken together, these results suggest that CD98 and CD99 may exert opposite effects on β1 integrin signaling through the regulation of FAK.…”

Section: Cd99 Attenuates Cd98-mediated β1 Integrin Signalingsupporting

confidence: 93%

“…Since a previous study suggested that amino acid transport may regulate CD98hc-mediated β1 integrin signaling by modulating RhoA activation [21], we examined whether crosslinking CD98hc could regulates the Na þ -independent amino acid transport. Crosslinking of CD98hc enhanced influx of L-[ 3 H]-leucine into MCF-7 cells to a certain degree ( Supplementary Fig.…”

Section: Cd99 Attenuates Cd98-mediated β1 Integrin Signalingmentioning

confidence: 99%

“…Previous studies indicated that CD98hc-induced FAK phosphorylation was dependent on the β1 integrin-mediated signaling pathway [17][18][19]. Recently, it is proposed that CD98hc contributes to tumorigenesis and skin homeostasis by modulating the extracellular matrix environment and the cellular responses through CD98hc/ integrins/RhoA/ROCK signaling pathway [20,21]. However, the precise mechanism by which CD98hc mediates β1 integrin signaling remains unclear.…”

Section: Introductionmentioning

confidence: 95%

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CD99 inhibits CD98-mediated β1 integrin signaling through SHP2-mediated FAK dephosphorylation

Lee

Yoo

Kim

et al. 2015

Experimental Cell Research

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Section: Cd99 Attenuates Cd98-mediated β1 Integrin Signalingsupporting

confidence: 93%

Section: Cd99 Attenuates Cd98-mediated β1 Integrin Signalingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

CD99 inhibits CD98-mediated β1 integrin signaling through SHP2-mediated FAK dephosphorylation

Lee

Yoo

Kim

et al. 2015

Experimental Cell Research

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“…CD98h plays an important role in amino-acid transport by interact with various types of transporter, such as LAT1 and xCT. LAT1 transports large neutral amino acids such as leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, methionine, and histidine, while xCT increases intracellular levels of cysteine (7,15,32). In the present study, metabolomic profiles suggested that intracellular amino acid concentrations and GSH were higher in CD98hc-expressing tissues, suggesting that CD98hc is associated with amino acid transport in gastric cancer tissues.…”

Section: Prognostic Role Of Cd98hc and Cd98 Amino Acid Transport In Gmentioning

confidence: 54%

CD44 variant 9 expression as a predictor for gastric cancer recurrence: immunohistochemical and metabolomic analysis of surgically resected tissues

et al. 2017

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CD44 variant 9 (CD44v9) and the heavy chain of 4F2 cell-surface antigen (CD98hc) appear important for regulation of reactive oxygen species defence and tumor growth in gastric cancer. This study examined the roles of CD44v9 and CD98hc as markers of gastric cancer recurrence, and investigated associations with energy metabolism. We applied capillary electrophoresis time-of-flight mass spectrometry to metabolome profiling of gastric cancer specimens from 103 patients who underwent resection with no residual tumor or microscopic residual tumor, and compared metabolite levels to immunohistochemical staining for CD44v9 and CD98hc. Positive expression rates were 40.7% for CD44v9 and 42.7% for CD98hc. Various tumor characteristics were significantly associated with CD44v9 expression. Five-year recurrence-free survival rate was significantly lower for CD44v9-positive tumors (39.1%) than for CD44v9-negative tumors (73.5%; P < 0.0001), but no significant differences in recurrence-free survival were seen according to CD98hc expression. Uniand multivariate analyses identified positive CD44v9 expression as an independent predictor of poorer recurrence-free survival. Metabolome analysis of 110 metabolites found that levels of glutathione disulfide were significantly lower and reduced glutathione (GSH)/ glutathione disulfide (GSSG) ratio was significantly higher in CD44v9-positive tumors than in CD44v9-negative tumors, suggesting that CD44v9 may enhance pentose phosphate pathway flux and maintain GSH levels in cancer cells.Gastric cancer is the fifth most common malignancy (952,000 cases in 2012) and the third leading cause of cancer-related deaths (723,000 deaths in 2012) worldwide (1). Despite the decline in global patient numbers, gastric cancer remains one of the most prevalent cancers in Japan. Although progress in early diagnosis and adjuvant therapy has improved outcomes for gastric cancer patients, radical surgery remains the primary approach for gastric cancer treatment. Outcomes are still unsatisfactory, because gastric cancers relapse with local or distant metastasis even after radical gastrectomy. More specific diagnostic and therapeutic targets are urgently needed to achieve better clinical applications in this field. CD44, a major adhesion molecule for the extracellular matrix, is a single-pass type I transmembrane protein that serves as a cell surface receptor for hyaluronic acid, and has been implicated in vari-

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“…K14-CreER T2 , CD98hc fl/fl have been described previously (11). The experiments have been performed on pure FVB/n background mice.…”

Section: Methodsmentioning

confidence: 99%

CD98hc (SLC3A2) Loss Protects Against Ras-Driven Tumorigenesis by Modulating Integrin-Mediated Mechanotransduction

et al. 2014

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CD98hc (SLC3A2) is the heavy chain component of the dimeric transmembrane glycoprotein CD98, which comprises the large neutral amino acid transporter LAT1 (SLC7A5) in cells. Overexpression of CD98hc occurs widely in cancer cells, and is associated with poor prognosis clinically, but its exact contributions to tumorigenesis are uncertain. In this study, we showed that that genetic deficiency of CD98hc protects against Ras-driven skin carcinogenesis. Deleting CD98hc after tumor induction was also sufficient to cause regression of existing tumors. Investigations into the basis for these effects defined two new functions of CD98hc that contribute to epithelial cancer beyond an intrinsic effect on CD98hc on tumor cell proliferation. First, CD98hc increased the stiffness of the tumor microenvironment. Second, CD98hc amplified the capacity of cells to respond to matrix rigidity, an essential factor in tumor development. Mechanistically, CD98hc mediated this stiffness-sensing by increasing Rho kinase (ROCK) activity, resulting in increased transcription mediated by YAP/TAZ, a nuclear relay for mechanical signals. Our results suggest that CD98hc contributes to carcinogenesis by amplifying a positive feedback loop which increases both extracellular matrix stiffness and resulting cellular responses. This work supports a rationale to explore the use of CD98hc inhibitors as cancer therapeutics,

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CD98hc (SLC3A2) regulation of skin homeostasis wanes with age

Cited by 18 publications

References 65 publications

CD99 inhibits CD98-mediated β1 integrin signaling through SHP2-mediated FAK dephosphorylation

CD99 inhibits CD98-mediated β1 integrin signaling through SHP2-mediated FAK dephosphorylation

<b>CD44 variant 9 expression as a predictor for gastric cancer recurrence: immunohistochemical and metabolomic analysis of surgically resected </b><b>tissues </b>

CD98hc (SLC3A2) Loss Protects Against Ras-Driven Tumorigenesis by Modulating Integrin-Mediated Mechanotransduction

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