Tspan5 is an independent favourable prognostic factor and suppresses tumour growth in gastric cancer

He, Panpan; Wang, Suihai; Zhang, Xuefeng; Gao, Yanjun; Niu, Wenbo; Dong, Ningning; Shi, Xiangyi; Geng, Yan; Ma, Qiang; Li, Ming; Jiang, Bo; Li, Jiliang

doi:10.18632/oncotarget.9514

Cited by 17 publications

(13 citation statements)

References 43 publications

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“…Interestingly, Tspan5 and Tspan15 differentially regulate the function of ADAM10 through a distinct membrane compartmentalization . The antagonistic effects between Tspan5 and Tspan15 have been also observed on cell proliferation since Tspan5 may inhibit the cell cycle whereas our study supports Tspan15 as activating the cell cycle. Recently, in vivo regulation of ADAM10 by Tspan15 has been shown .…”

Section: Discussionmentioning

confidence: 99%

Tspan15 Is a New Stemness‐Related Marker in Hepatocellular Carcinoma

et al. 2019

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Hepatocellular carcinoma (HCC) is the second cause of cancer‐related deaths worldwide. A clearer understanding of the molecular mechanisms underlying tumor growth and invasiveness remains crucial for developing new therapies. Here, the expression of tetraspanins, a family of plasma membrane organizers involved in tumor progression, has been addressed. Integrative approaches combining transcriptomics and bioinformatics allow demonstrating the induced and heterogeneous expression of Tspan15 in HCC. Tspan15 positive tumors exhibit signatures related to hepatic progenitor cells as well as recurrence of cancer. Immunohistochemistry experiments confirm Tspan15 expression in the subset of HCC expressing stemness‐related markers such as EpCAM and Cytokeratin‐19. Functional networks reveal that most of these genes expressed in correlation to Tspan15 support cell proliferation. Furthermore, Tspan15 overexpression in the hepatoma cell line HepG2 significantly increases cell proliferation. A quantitative proteomic analysis of the secretome reveals a higher abundance of the protein connective tissue growth factor (CTGF), a pleiotropic matricellular signaling protein. Proteomic profiling of Tspan15 complexes allows identifying numerous membrane proteins including several growth factor receptors. Finally, Tspan15 increases ERK1/2 phosphorylation that directly controls CTGF expression and secretion. In conclusion, Tspan15 is a new stemness‐related marker in HCC which exhibits high potential of tumor growth and recurrence.

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Section: Discussionmentioning

confidence: 99%

Tspan15 Is a New Stemness‐Related Marker in Hepatocellular Carcinoma

et al. 2019

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“…Previous studies demonstrated that TSPAN5 can regulate the function of ADAM10 on the cell surface and promote ADAM10‐mediated degradation of CD44 39 . Studies have also shown that TSPAN5 acts as a proapoptotic factor that inhibits tumor growth in gastric cancer 40 . On the other hand, TSPAN5 is positively regulated by the Notch signaling pathway 41 .…”

Section: Discussionmentioning

confidence: 99%

“…39 Studies have also shown that TSPAN5 acts as a proapoptotic factor that inhibits tumor growth in gastric cancer. 40 On the other hand, TSPAN5 is positively regulated by the Notch signaling pathway. 41 In this report, TSPAN5 was found to be poorly expressed in BCSCs, and overexpression of TSPAN5 abrogated miR-155-induced changes in stemness and DCA resistance in TNBC cells.…”

Section: Discussionmentioning

confidence: 99%

miR‐155 increases stemness and decitabine resistance in triple‐negative breast cancer cells by inhibiting TSPAN5

Yang

Xian-jin

Liang

et al. 2020

Molecular Carcinogenesis

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Effective therapeutic targets for triple‐negative breast cancer (TNBC), a special type of breast cancer (BC) with rapid metastasis and poor prognosis, are lacking, especially for patients with chemotherapy resistance. Decitabine (DCA) is a Food and Drug Administration‐approved DNA methyltransferase inhibitor that has been proven effective for the treatment of tumors. However, its antitumor effect in cancer cells is limited by multidrug resistance. Cancer stem cells (CSCs), which are thought to act as seeds during tumor formation, regulate tumorigenesis, metastasis, and drug resistance through complex signaling. Our previous study found that miR‐155 is upregulated in BC, but whether and how miR‐155 regulates DCA resistance is unclear. In this study, we demonstrated that miR‐155 was upregulated in CD24−CD44+ BC stem cells (BCSCs). In addition, the overexpression of miR‐155 increased the number of CD24−CD44+ CSCs, DCA resistance and tumor clone formation in MDA‐231 and BT‐549 BC cells, and knockdown of miR‐155 inhibited DCA resistance and stemness in BCSCs in vitro. Moreover, miR‐155 induced stemness and DCA resistance by inhibiting the direct target gene tetraspanin‐5 (TSPAN5). We further confirmed that overexpression of TSPAN5 abrogated the effect of miR‐155 in promoting stemness and DCA resistance in BC cells. Our data show that miR‐155 increases stemness and DCA resistance in BC cells by targeting TSPAN5. These data provide a therapeutic strategy and mechanistic basis for future possible clinical applications targeting the miR‐155/TSPAN5 signaling axis in the treatment of TNBC.

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“…26 However, accumulation evidence has suggested that potent GSIs were effective to inhibit γ-secretase activity in GC cell lines but were limited in their ability to induce apoptosis. 27 What about CCL? What about the combination of CCL and Notch pathway inhibitors?…”

Section: Discussionmentioning

confidence: 99%

Crocodile choline fromCrocodylus siamensisinduces apoptosis of human gastric cancer

Mao

et al. 2017

Tumour Biol.

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Crocodile choline, an active compound isolated from Crocodylus siamensis, was found to exert potent anti-cancer activities against human gastric cancer cells in vitro and in vivo. Our study revealed that crocodile choline led to cell cycle arrest at the G2/M phase through attenuating the expressions of cyclins, Cyclin B1, and CDK-1. Furthermore, crocodile choline accelerated apoptosis through the mitochondrial apoptotic pathway with the decrease in mitochondrial membrane potential, the increase in reactive oxygen species production and Bax/Bcl-2 ratio, and the activation of caspase-3 along with the release of cytochrome c. In addition, this study, for the first time, shows that Notch pathway is remarkably deregulated by crocodile choline. The combination of crocodile choline and Notch1 short interfering RNA led to dramatically increased cytotoxicity than observed with either agent alone. Notch1 short interfering RNA sensitized and potentiated the capability of crocodile choline to suppress the cell progression and invasion of gastric cancer. Taken together, these data suggested that crocodile choline was a potent progression inhibitor of gastric cancer cells, which was correlated with mitochondrial apoptotic pathway and Notch pathway. Combining Notch1 inhibitors with crocodile choline might represent a novel approach for gastric cancer.

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Tspan5 is an independent favourable prognostic factor and suppresses tumour growth in gastric cancer

Cited by 17 publications

References 43 publications

Tspan15 Is a New Stemness‐Related Marker in Hepatocellular Carcinoma

Tspan15 Is a New Stemness‐Related Marker in Hepatocellular Carcinoma

miR‐155 increases stemness and decitabine resistance in triple‐negative breast cancer cells by inhibiting TSPAN5

Crocodile choline fromCrocodylus siamensisinduces apoptosis of human gastric cancer

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