Alternative splicing of KAI1 abrogates its tumor-suppressive effects on integrin αvβ3-mediated ovarian cancer biology

Upheber, Sina; Karle, Alexandra Lisa; Miller, Julia M.; Schlaugk, S; Groß, Eva; Reuning, Ute

doi:10.1016/j.cellsig.2014.11.028

Cited by 18 publications

(30 citation statements)

References 74 publications

(127 reference statements)

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“…A splicing variant encodes C-terminal truncated CD82 proteins that no longer inhibit invasion of colon cancer cells and even promote migration of ovarian cancer cells [11,95]. Importantly, this splicing variant is present or sometimes expressed higher in the metastatic tissues of human gastric or ovarian cancer, respectively [11,95].…”

Section: The Loss and Mutation Of The Cd82 Genementioning

confidence: 99%

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Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

Feng

Huang

Wren

et al. 2015

Cancer Metastasis Rev

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Tetraspanin CD82 suppresses the progression and metastasis of a wide range of solid malignant tumors. However, its roles in tumorigenesis and hematopoietic malignancy remain unclear. Ubiquitously expressed CD82 restrains cell migration and cell invasion by modulating both cell-matrix and cell-cell adhesiveness and confining outside-in pro-motility signaling. This restraint at least contributes to, if not determines, the metastasis-suppressive activity and, also likely, the physiological functions of CD82. As a modulator of cell membrane heterogeneity, CD82 alters microdomains, trafficking, and topography of the membrane by changing the membrane molecular landscape. The functional activities of membrane molecules and the cytoskeletal interaction of the cell membrane are subsequently altered, followed by changes in cellular functions. Given its pathological and physiological importance, CD82 is a promising candidate for clinically predicting and blocking tumor progression and metastasis and also an emerging model protein for mechanistically understanding cell membrane organization and heterogeneity.

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Section: The Loss and Mutation Of The Cd82 Genementioning

confidence: 99%

“…Importantly, this splicing variant is present or sometimes expressed higher in the metastatic tissues of human gastric or ovarian cancer, respectively [11,95].…”

Section: The Loss and Mutation Of The Cd82 Genementioning

confidence: 99%

Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

Feng

Huang

Wren

et al. 2015

Cancer Metastasis Rev

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“…Similar to other epithelial cancers, cell adhesion molecules must play a role in the progression of ovarian cancer, especially since aberrant expression of various CAMs, such as mucins [11], integrins [12], CD44 [13], L1CAM [14], cadherin [15], claudins [16], EpCAM [17], ALCAM [18] and METCAM/MUC18 [19,20], has been associated with the malignant progression of ovarian cancer. Some of the CAMs may play a positive role, such as MUC4 [21], CD44 [22], L1CAM [23], ALCAM [18], and P-cadherin [24]; however, some a negative role, such as β3-integrin [25], E-cadherin [26], claudin-3, 4, &7 [27], EpCAM [28], and KAI1 [29], in the progression of ovarian cancer cells. We have been focusing our studies on the role of METCAM/MUC18 in the progression of several epithelial tumors, including epithelial ovarian tumors [30].…”

Section: Cell Adhesion Molecules and The Progression Of Ovarian Cancermentioning

confidence: 99%

METCAM/MUC18 plays a Novel Tumor and Metastasis Suppressor Role in the Progression of Human Ovarian Cancer Cells

Wu¹

2017

OGIJ

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METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Iglike gene super-family, is capable of performing typical functions of CAMs, such as mediating cell-cell and cell-extracellular interactions, crosstalk with intracellular signaling pathways, and modulating social behaviors of cells. The role of METCAM/ MUC18 in the progression of ovarian cancer cells has not been well studied. Previous studies showed that METCAM/MUC18 is expressed in normal ovarian epithelial cells, but expressed at higher levels in ovarian cancer tissues, suggesting that METCAM/ MUC18 may serve as a biomarker for the malignant progression of clinical ovarian cancers and it has been implicated for playing a positive role in the progression of the cancer. Recently we provided evidence from in vitro and in vivo studies to suggest that the above notion is a fortuitous correlation and that METCAM/MUC18 actually serves as a tumor and metastasis suppressor for the malignant progression of ovarian cancer cells, similar to its role in the malignant progression of one mouse melanoma cell line and nasopharyngeal carcinoma type I. Many possible mechanisms mediated by this CAM during early tumor development and metastasis are suggested. Furthermore, we suggest that METCAM/MUC18 may be used a therapeutic reagent to arrest the malignant progression of clinical ovarian cancer.

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“…Recently, it was reported that no co-localization was observed between a KAI1 splice variant and E-cadherin. Moreover, this KAI1 variant promotes tumor progression and cancer metastasis (11). Besides, KAI1 could regulate MMP-2 and MMP-9 level in patients with endometrial cancer.…”

Section: Introductionmentioning

confidence: 99%

Nm23-H1 was involved in regulation of KAI1 expression in high-metastatic lung cancer cells L9981

et al. 2016

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Background:The tetraspanin KAI1/CD82 was identified as a tumor metastasis suppressor that downregulated in malignant progression of lung cancer. However, the underlying mechanism of anti-metastasis role of KAI1 in lung cancer is hardly known. In this paper, we sought to study the function and regulatory mechanism of KAI1 in high metastasis lung cancer cell line.Methods: KAI1 expression was detected in high/low metastatic large lung cancer cell line L9981/NL9980 by quantitative real-time polymerase chain reaction (qRT-PCR). The tumor suppressor function of KAI1 was determined by wound healing assay after over-expression or knockdown of KAI1 in L9981 or NL9980 cells.Invasion assay was performed to detect the invasion ability of L9981 by transfection of KAI1. The effect of tumor suppressor p53 on KAI1 expression was measured by western blot and luciferase assay. Then the regulation of KAI1 due to over-expression of metastasis suppressor nm23-H1 was monitored by qRT-PCR, western blot and reporter gene assay. The progression of L9981 cells after p53 and nm23-H1 expression was detected by invasion assay. Also, methylation status of KAI1 promoter in NL9980 and L9981 cells were examined by bisulfite sequencing and methylation-specific PCR.Results: We found that KAI1 is down-regulated in high metastatic L9981 cells compare with NL9980 cells. The migration and invasion of L9981 cells were remarkably suppressed in vitro by KAI1 transfection.The migration ability of NL9980 was enhanced by inhibition of KAI1. Furthermore, KAI1 expression was induced after over-expression of p53 or nm23-H1, while cell invasion was inhibited in L9981 cells. The results of reporter analysis indicated that KAI1 promoter region between −922 to −846 could response to nm23-H1. In addition, we discovered only slight methylation of KAI1 promoter, which showed that loss expression of KAI1 in L9981 cells may not due to promoter methylation. Conclusions:The results suggested that nm23-H1 was involved in the KAI1-regulated inhibition of metastasis in lung cancer cells. More insights into the relationship between KAI1 and other metastasis suppressors will pave the way for the elucidation of anti-metastasis mechanism in lung cancer.

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Alternative splicing of KAI1 abrogates its tumor-suppressive effects on integrin αvβ3-mediated ovarian cancer biology

Cited by 18 publications

References 74 publications

Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

METCAM/MUC18 plays a Novel Tumor and Metastasis Suppressor Role in the Progression of Human Ovarian Cancer Cells

Nm23-H1 was involved in regulation of KAI1 expression in high-metastatic lung cancer cells L9981

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