Sorting nexin 10 acts as a tumor suppressor in tumorigenesis and progression of colorectal cancer through regulating chaperone mediated autophagy degradation of p21Cip1/WAF1

Zhang, Sulin; Hu, Bin; You, Yun; Yang, Zhiwen; Liu, Lixin; Tang, Huanhuan; Bao, Weilian; Guan, Yunyun; Shen, X. Y.

doi:10.1016/j.canlet.2018.01.045

Cited by 40 publications

(43 citation statements)

References 38 publications

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“…How SNX5 is involved in tube formation is unknown. Other members of sorting nexin family, sorting nexin 1 (SNX1) and sorting nexin 10 (SNX10) have been shown to act as tumor suppressors of colorectal cancers (Bian et al, ; Huang et al, ; Le et al, ; Nguyen et al, ; Zhang et al, ). Both mRNA and protein levels of SNX1 were significantly decreased in human colorectal cancer tissues (Nguyen et al, ).…”

Section: Discussionmentioning

confidence: 99%

SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9

Tanigawa

Maekawa

Kiyoi

et al. 2019

Journal Cellular Physiology

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Angiogenesis, the formation of new blood vessels, is involved in a variety of diseases including the tumor growth. In response to various angiogenic stimulations, a number of proteins on the surface of vascular endothelial cells are activated to coordinate cell proliferation, migration, and spreading processes to form new blood vessels. Plasma membrane localization of these angiogenic proteins, which include vascular endothelial growth factor receptors and integrins, are warranted by intracellular membrane trafficking. Here, by using a siRNA library, we screened for the sorting nexin family that regulates intracellular trafficking and identified sorting nexin 9 (SNX9) as a novel angiogenic factor in human umbilical vein endothelial cells (HUVECs). SNX9 was essential for cell spreading on the Matrigel, and tube formation that mimics in vivo angiogenesis in HUVECs. SNX9 depletion significantly delayed the recycling of integrin β1, an essential adhesion molecule for angiogenesis, and reduced the surface levels of integrin β1 in HUVECs. Clinically, we showed that SNX9 protein was highly expressed in tumor endothelial cells of human colorectal cancer tissues. High‐level expression of SNX9 messenger RNA significantly correlated with poor prognosis of the patients with colorectal cancer. These results suggest that SNX9 is an angiogenic factor and provide a novel target for the development of new antiangiogenic drugs.

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Section: Discussionmentioning

confidence: 99%

SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9

Tanigawa

Maekawa

Kiyoi

et al. 2019

Journal Cellular Physiology

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“…Although there are no studies on how CMA is regulated in GB cells, it is interesting to consider that mechanisms of CMA up-regulation in some cancer cells are the same as in non-transformed cells [95,96]. In fact, during starvation, normal cells increase the levels of lysosomal LAMP2A by reducing its lysosomal turnover [97], and in a same way, colorectal cancer cells up-regulate LAMP2A by reducing their degradation through lowering levels of sorting nexin 10 (SNX10) [95]. Conversely, other cancer cells use similar mechanisms as healthy cells, but with different results [98].…”

Section: Regulationmentioning

confidence: 99%

Autophagy in the Immunosuppressive Perivascular Microenvironment of Glioblastoma

Molina

García‐Bernal

Valdor

2019

Cancers

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Glioblastoma (GB) has been shown to up-regulate autophagy with anti- or pro-oncogenic effects. Recently, our group has shown how GB cells aberrantly up-regulate chaperone-mediated autophagy (CMA) in pericytes of peritumoral areas to modulate their immune function through cell-cell interaction and in the tumor’s own benefit. Thus, to understand GB progression, the effect that GB cells could have on autophagy of immune cells that surround the tumor needs to be deeply explored. In this review, we summarize all the latest evidence of several molecular and cellular immunosuppressive mechanisms in the perivascular tumor microenvironment. This immunosuppression has been reported to facilitate GB progression and may be differently modulated by several types of autophagy as a critical point to be considered for therapeutic interventions.

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“…Ectopic expression of LAMP-2C in melanomas disrupted CMA, as indicated by the accumulation of several proteins typically degraded by CMA including Chk1, IκBα, and p21 (Cuervo et al, 1998; Park et al, 2015; Zhang et al, 2018). Studies have described an intricate cross-communication and compensatory mechanisms among the different autophagic pathways and the proteasome (Park and Cuervo, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…In the melanoma cell line DM331, ectopic expression of LAMP-2C resulted in decreased expression of LAMP-2A and LAMP-2B proteins. CMA was diminished in cells with increased LAMP-2C, as indicated by the increased abundance of several proteins typically targeted for degradation by CMA including Chk1, IκBα, and p21 (Cuervo et al, 1998; Park et al, 2015; Zhang et al, 2018). Significant reductions in MA were also detected in melanomas with increased LAMP-2C expression based on analysis of MA flux and autophagosome abundance.…”

Section: Introductionmentioning

confidence: 99%

Melanoma LAMP-2C Modulates Tumor Growth and Autophagy

Pérez

Sinn

Sandusky

et al. 2018

Front. Cell Dev. Biol.

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Autophagy plays critical but diverse roles in cellular quality control and homeostasis potentially checking tumor development by removing mutated or damaged macromolecules, while conversely fostering tumor survival by supplying essential nutrients during cancer progression. This report documents a novel inhibitory role for a lysosome-associated membrane protein, LAMP-2C in modulating autophagy and melanoma cell growth in vitro and in vivo. Solid tumors such as melanomas encounter a variety of stresses in vivo including inflammatory cytokines produced by infiltrating lymphocytes directed at limiting tumor growth and spread. Here, we report that in response to the anti-tumor, pro-inflammatory cytokine interferon-gamma, melanoma cell expression of LAMP2C mRNA significantly increased. These results prompted an investigation of whether increased melanoma cell expression of LAMP-2C might represent a mechanism to control or limit human melanoma growth and survival. In this study, enhanced expression of human LAMP-2C in melanoma cells perturbed macroautophagy and chaperone-mediated autophagy in several human melanoma lines. In vitro analysis showed increasing LAMP-2C expression in a melanoma cell line, triggered reduced cellular LAMP-2A and LAMP-2B protein expression. Melanoma cells with enhanced LAMP-2C expression displayed increased cell cycle arrest, increased expression of the cell cycle regulators Chk1 and p21, and greater apoptosis and necrosis in several cell lines tested. The increased abundance of Chk1 protein in melanoma cells with increased LAMP-2C expression was not due to higher CHEK1 mRNA levels, but rather an increase in Chk1 protein abundance including Chk1 molecules phosphorylated at Ser345. Human melanoma cell xenografts with increased LAMP-2C expression, displayed reduced growth in immune compromised murine hosts. Melanomas with high LAMP-2C expression showed increased necrosis and reduced cell density upon histological analysis. These results reveal a novel role for LAMP-2C in negatively regulating melanoma growth and survival.

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Sorting nexin 10 acts as a tumor suppressor in tumorigenesis and progression of colorectal cancer through regulating chaperone mediated autophagy degradation of p21Cip1/WAF1

Cited by 40 publications

References 38 publications

SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9

SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9

Autophagy in the Immunosuppressive Perivascular Microenvironment of Glioblastoma

Melanoma LAMP-2C Modulates Tumor Growth and Autophagy

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