ライフサイエンスコーパス: KAI1

1 s in the tumor suppressor genes pRB, p53 and KAI1.

2 D11S1344, which is located in the region of KAI1.

3 argely blocked by concomitant suppression of KAI1.

4 nown as gp-Fy), as an interacting partner of KAI1.

5 The product of CD82 is KAI1, a 40- to 75-kDa tetraspanin cell-surface protein a

6 Suppression of gp78 increases KAI1 abundance and reduces the metastatic potential of t

7 ets the transmembrane metastasis suppressor, KAI1 (also known as CD82), for degradation.

8 ial cells through direct interaction between KAI1 and DARC, and that this interaction leads to inhibi

9 dies of the tumor metastasis suppressor gene KAI1 and plasminogen activator inhibitor 1 (PAI1), defin

10 Comparisons of gene structures between KAI1 and seven other members of the transmembrane 4 supe

11 of the percentage of cells that stained for KAI1 and the intensity of the stain (1, 2, or 3).

12 ns of TGF-beta receptors, E-cadherin, C-CAM, KAI1, and some integrins have an inverse correlation wit

13 ts indicate that the cancer cells expressing KAI1 attach to vascular endothelial cells through direct

14 NDRG1 and KAI1 belong to metastasis suppressor genes, which impede

15 The transmembrane 4 superfamily member KAI1 (CD82) has been shown to inhibit pulmonary metastas

16 ovement, but not for the association between KAI1/CD82 and alpha3beta1 integrin.

17 events critical for motility are altered by KAI1/CD82 and how KAI1/CD82 regulates these events.

18 on regulates the subcellular distribution of KAI1/CD82 and its association with other tetraspanins, s

19 l-surface protein physically associated with KAI1/CD82 and named it KASP: a KAI1/CD82-associated surf

20 s are needed for proper interactions between KAI1/CD82 and tetraspanins CD9 and CD151, which also reg

21 Distinctive from known KAI1/CD82 associations that usually occur in the context

22 Cancer metastasis suppressor KAI1/CD82 belongs to the tetraspanin superfamily and inv

23 AI1/CD82, overexpression of p130CAS in Du145-KAI1/CD82 cells increased the formation of p130CAS-CrkII

24 witch" in cell motility, was formed in Du145-KAI1/CD82 cells.

25 nd Lyn, however, remained unchanged in Du145-KAI1/CD82 cells.

26 In transmembrane (TM) domains, tetraspanin KAI1/CD82 contains an Asn, a Gln, and a Glu polar residu

27 erent tetraspanins, and its association with KAI1/CD82 could be independent of CD81 and CD9.

28 ctin reorganization; at the molecular level, KAI1/CD82 deregulated Rac1, RhoA, and their effectors co

29 for the functional integrity of tetraspanin KAI1/CD82 during the suppression of cancer cell migratio

30 Upon KAI1/CD82 expression, Rac effector cofilin was not enric

31 of the plasma membrane became deficient upon KAI1/CD82 expression.

32 egulated at both RNA and protein levels upon KAI1/CD82 expression.

33 tions of microprotrusion and microvesicle to KAI1/CD82 function.

34 Furthermore, EWI2/PGRL synergizes KAI1/CD82 in inhibiting cell migration, indicating that

35 In summary, at the cellular level KAI1/CD82 inhibited polarized protrusion and retraction

36 Notably, KAI1/CD82 inhibits the formation of microprotrusions and

37 Hence, KAI1/CD82 interacts with tetraspanin and integrin by dif

38 The cancer metastasis suppressor protein KAI1/CD82 is a member of the tetraspanin superfamily.

39 Tumor metastases suppressor protein KAI1/CD82 is capable of blocking the tumor metastases wi

40 ive (+) cells, we found that the tetraspanin KAI1/CD82 is far more highly expressed in adult O4(+) ce

41 otility seen in the palmitoylation-deficient KAI1/CD82 mutant correlates with regaining of p130(CAS)-

42 Notably, the palmitoylation-deficient KAI1/CD82 mutant largely reversed the wild-type KAI1/CD8

43 Moreover, we found that KAI1/CD82 palmitoylation affected motility-related subce

44 KAI1/CD82 protein is a member of the tetraspanin superfa

45 or motility are altered by KAI1/CD82 and how KAI1/CD82 regulates these events.

46 However, KAI1/CD82 still efficiently inhibits cell migration when

47 line Du145 was substantially inhibited when KAI1/CD82 was expressed.

48 In this study, we found that tetraspanin KAI1/CD82 was palmitoylated when expressed in PC3 metast

49 suggesting that the localized interaction of KAI1/CD82 with tetraspanin webs or tetraspanin-enriched

50 kII coupling, a signaling step important for KAI1/CD82's activity.

51 ion of these processes likely contributes to KAI1/CD82's inhibition of motility.

52 1/CD82 mutant largely reversed the wild-type KAI1/CD82's inhibitory effects on migration and invasion

53 panin-enriched microdomains is important for KAI1/CD82's motility-inhibitory activity.

54 KAI1/CD82, a tetraspanin protein, was first identified a

55 To determine how tetraspanin KAI1/CD82, a tumor metastasis suppressor, inhibits cell

56 Rac1 activity was reduced by KAI1/CD82, consistent with the diminution of lamellipodi

57 ctor-stimulated RhoA activity was blocked by KAI1/CD82, consistent with the loss of stress fiber and

58 ons maintain the conformational stability of KAI1/CD82, evidenced by the facts that the mutant is mor

59 Consistent with the wide distribution of KAI1/CD82, KASP is expressed ubiquitously in human tissu

60 eed important for the motility inhibition by KAI1/CD82, overexpression of p130CAS in Du145-KAI1/CD82

61 ion, homodimerization, and global folding of KAI1/CD82, the TM interactions maintain the conformation

62 In summary, we identified a major KAI1/CD82-associated protein, EWI2/PGRL, that is importa

63 sociated with KAI1/CD82 and named it KASP: a KAI1/CD82-associated surface protein.

64 We found that KAI1/CD82-expressing cells typically exhibited elongated

65 FAK-Lyn-p130CAS-CrkII pathway is altered in KAI1/CD82-expressing cells, and 2) p130CAS-CrkII couplin

66 ame less detectable at the cell periphery in KAI1/CD82-expressing cells.

67 Moreover, KAI1/CD82-induced phenotypes likely resulted from the su

68 cur in the context of "tetraspanin web," the KAI1/CD82-KASP association is likely to be direct becaus

69 30CAS-CrkII complex and largely reversed the KAI1/CD82-mediated inhibition of cell motility.

70 The mechanism of KAI1/CD82-mediated metastasis suppression remains unclea

71 ed protein, EWI2/PGRL, that is important for KAI1/CD82-mediated suppression of cancer cell migration.

72 The mechanism of KAI1/CD82-mediated suppression of cancer metastasis rema

73 nd 2) p130CAS-CrkII coupling is required for KAI1/CD82-mediated suppression of cell motility.

74 nge are needed for the intrinsic activity of KAI1/CD82.

75 n-, and metastasis-suppressive activities of KAI1/CD82.

76 protein was decreased upon the expression of KAI1/CD82.

77 transmembrane proteins that associates with KAI1/CD82.

78 /PGRL is likely required for the function of KAI1/CD82.

79 n in breast cancer, we transfected the human KAI1 cDNA into two highly malignant breast cancer cell l

80 y compromised in DARC knockout mice, whereas KAI1 completely abrogated pulmonary metastasis in wild-t

81 r, in vitro and in vivo studies identify the KAI1-DARC interaction as a potential target for cancer t

82 = 18), and cervix (n = 14) showed extensive KAI1 down-regulation.

83 We found no correlation between loss of KAI1 expression and stage of disease.

84 We also investigated the relationship of KAI1 expression and two other transmembrane four superfa

85 Reduced KAI1 expression associates with malignant progression of

86 lls expressing KAI1, whereas cells that lost KAI1 expression can proliferate, potentially giving rise

87 strated the utility of our assay by studying KAI1 expression in 34 lymphoid and 57 squamous lesions.

88 lish an immunohistochemical method to detect KAI1 expression in archival tissues.

89 istry is a suitable technique for evaluating KAI1 expression in archival tissues; (ii) KAI1 was not e

90 The purpose of our study was to investigate KAI1 expression in the progression of human colorectal c

91 In 10 patients, we also noted loss of KAI1 expression in the transition from normal colonic mu

92 was accompanied with significant decrease in KAI1 expression in vitro and in vivo.

93 KAI1 expression is decreased in the progression of commo

94 To determine whether KAI1 expression is responsible for the metastasis suppre

95 Moreover, loss of KAI1 expression significantly abrogated NDRG1-mediated m

96 Furthermore, KAI1 expression significantly suppressed the in vitro ce

97 High KAI1 expression significantly suppressed the metastatic

98 Loss of KAI1 expression was also found in a subset of 10 high-gr

99 Previously, we have demonstrated that KAI1 expression was down-regulated in metastatic breast

100 31, which both have low levels of endogenous KAI1 expression.

101 we observed a progressive down-regulation of KAI1, from the normal adjacent colonic mucosa (KMS 193)

102 The expression of the KAI1 gene also is found to be down-regulated during the

103 uppressor gene p53 can directly activate the KAI1 gene by interacting with the 5' upstream region.

104 sion of NDRG1 was able to augment endogenous KAI1 gene expression in prostate cancer cell lines, wher

105 gulatory mechanism for the expression of the KAI1 gene in human tissues.

106 gulatory mechanism for the expression of the KAI1 gene in normal and cancerous tissues, we characteri

107 The transcription initiation site of the KAI1 gene is located 181 bp upstream of the first nucleo

108 e tumors revealed that the expression of the KAI1 gene was correlated strongly to that of the p53 gen

109 The KAI1 gene, located on human chromosome 11p11.2, suppress

110 out 80 kb of DNA was identified as the human KAI1 gene, which contains 8 kb of 5'-region, 10 exons, 9

111 cancer, leads to the down-regulation of the KAI1 gene, which may result in the progression of metast

112 d transcription initiation site of the human KAI1 gene.

113 volve either mutation or allelic loss of the KAI1 gene.

114 hat ATF3 indeed bound to the promoter of the KAI1 gene.

115 TF3 expression followed by activation of the KAI1 gene.

116 dicate a direct relationship between p53 and KAI1 genes and suggest that the loss of p53 function, wh

117 Downregulation of KAI1 has been found to be clinically associated with met

118 (iii) there was extensive down-regulation of KAI1 in squamous cell carcinomas, suggestive of an impor

119 ment to the endothelial cell surface whereby KAI1 interacts with the Duffy antigen receptor for chemo

120 KAI1 is a metastasis suppressor gene for human prostate

121 KAI1 is a metastasis suppressor gene on human chromosome

122 KAI1 is a tumor metastasis suppressor gene that is capab

123 Surprisingly, KAI1 is also directly activated by a ternary complex, de

124 Using cell lines with known KAI1 levels and paraffin-embedded KAI1 positive tissues

125 KAI1 may also have post-translational modifications spec

126 melanocytes by Western blot to determine if KAI1 may be involved in multiple cancers.

127 Our results suggested that KAI1 may function as a negative regulator of breast canc

128 Each tissue section was assigned a KAI1 mean score (KMS) from 0 to 300 based on the product

129 Decreased expression of the human KAI1 metastasis-suppressor gene is involved in the progr

130 nking each exon of KAI1 were used to analyze KAI1 mutation and allelic loss by the method of PLR-sing

131 five of 13 diffuse large cell lymphomas were KAI1 negative.

132 To evaluate whether dysregulation of KAI1 occurs during the progression of human prostatic ca

133 We conclude that the down-regulation of KAI1 occurs early in the progression of colorectal cance

134 mical analysis showed that loss of NDRG1 and KAI1 occurs in parallel as prostate cancer progresses.

135 with known KAI1 levels and paraffin-embedded KAI1 positive tissues as controls, we observed strong me

136 All eight reactive lymph nodes were KAI1 positive.

137 Further analysis revealed that the KAI1 promoter contained a consensus binding motif of ATF

138 epressor of gene transcription with LRP1 and KAI1 promoters.

139 immunohistochemical staining, high levels of KAI1 protein are detected in the epithelial but not stro

140 ndometrial cells had distinct, heterogeneous KAI1 protein band patterns in Western blots that were du

141 We also investigated KAI1 protein expression by immunohistochemistry in tissu

142 These results demonstrate that KAI1 protein expression is consistently down-regulated d

143 KAI1 protein expression is downregulated in more than 70

144 ncers had downregulation, with 60% having no KAI1 protein expression.

145 We analysed KAI1 protein in normal and cancer cells of the prostate,

146 lung and pancreatic cancers, but the role of KAI1 protein in the malignant progression of other human

147 In epithelial cells, KAI1 protein is expressed on the plasma membrane.

148 Downregulation of KAI1 protein may be an indicator of metastatic potential

149 such untreated patients, down-regulation of KAI1 protein occurred in all of the lymph node metastase

150 We found that KAI1 protein was downregulated in 31/42 of the cancer ce

151 ular mechanism of the suppressor function of KAI1 remains elusive.

152 Overexpression of KAI1 results in metastasis suppression in certain highly

153 Our model of the mechanism of action of KAI1 shows that metastasis suppressor activity can be de

154 Here we report that tetraspanin CD82/KAI1 specifically suppresses ubiquitylation of EGFR afte

155 45 cells appears independent of p53, pRB and KAI1 status.

156 nteraction with host tissue and explains how KAI1 suppresses metastasis without affecting primary tum

157 ulated genes, exemplified by the tetraspanin KAI1 that regulates membrane receptor function.

158 -based analysis revealed that ATF3 modulated KAI1 transcription through cooperation with other endoge

159 Parental, vector-only transfectants and KAI1 transfectant clones were injected into the mammary

160 antly suppressed the metastatic potential of KAI1-transfected LCC6 cells.

161 tly suppressed the in vitro cell invasion in KAI1-transfected MDA-MB-231 cells.

162 In 84 patients with colorectal cancer, KAI1 was expressed at high levels in normal colonic muco

163 KAI1 was expressed heterogeneously, with the tumor cell

164 KAI1 was highly expressed in the primary SW480 colon can

165 The metastasis suppressor gene KAI1 was identified by its ability to inhibit the format

166 ng KAI1 expression in archival tissues; (ii) KAI1 was not expressed in a subset of both low-grade and

167 more, the metastasis-suppression activity of KAI1 was significantly compromised in DARC knockout mice

168 pha to the promoter of an APPct target gene (KAI1) was demonstrated.

169 loning, a metastatic suppressor gene, termed KAI1, was identified, which is located at human chromoso

170 CD82, also known as KAI1, was recently identified as a prostate cancer metas

171 To define the mechanism of action of KAI1, we used a yeast two-hybrid screen and identified a

172 in expression, mutation, and allelic loss of KAI1 were analyzed using a tissue bank of 98 primary can

173 ved from the sequences flanking each exon of KAI1 were used to analyze KAI1 mutation and allelic loss

174 senescent signal to cancer cells expressing KAI1, whereas cells that lost KAI1 expression can prolif

175 f two metastasis suppressor genes, NDRG1 and KAI1, which together concerted metastasis-suppressive ac