SNX10 (sorting nexin 10) inhibits colorectal cancer initiation and progression by controlling autophagic degradation of SRC

Zhang, Sulin; Yang, Zhiwen; Bao, Weilian; Liu, Lixin; You, Yun; Wang, Xu; Shao, Liming; Fu, Wei; Kou, Xinhui; Shen, Weixing; Yuan, Congmin; Hu, Bin; Dang, Wen-Zhen; Nandakumar, Kutty Selva; Jiang, Hualiang; Zheng, Mingyue; Shen, X. Y.

doi:10.1080/15548627.2019.1632122

Cited by 44 publications

(44 citation statements)

References 41 publications

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“…mRNAs play an important regulatory role in numerous biological processes, tumorigenesis, and development (20). Recent publications have revealed that SNX10 (21) and SMAD4 (22) act as tumor suppressors in CRC and could be potential therapeutic targets. CP1 (23) and ANG2 (24) were associated with promoting tumor progression and metastasis and may be useful targets for cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

Identification Hub Genes in Colorectal Cancer by Integrating Weighted Gene Co-Expression Network Analysis and Clinical Validation in vivo and vitro

et al. 2020

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Colorectal cancer (CRC) is the third leading cause of death in the world. However, the key roles of most molecules in CRC remain unclear. This study aimed to identify key modules and hub genes associated with the progression of CRC. The data of the patients with CRC were obtained from the Gene Expression Omnibus (GEO) database and assessed by weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses performed in R. by WGCNA, several hub genes that regulate the mechanism of tumorigenesis in CRC were identified, which were associated with clinical traits. Next, we screened hub genes related to the progression of CRC authenticated by The Cancer Genome Atlas (TCGA) and Oncomine databases. Three hub genes (HCLS1, EVI2B, and CD48) were identified, and survival analysis was further performed. Moreover, the results of qPCR and immunohistochemistry staining revealed that HCLS1, EVI2B, and CD48 are tumor suppressor genes. Further, the functional study verified that over-expression of HCLS1, EVI2B, and CD48 can reduce the proliferation, migration, and invasion ability of CRC cells and significantly suppress CRC tumor growth in vivo. In summary, we identified three hub genes that were associated with the progression of CRC that can be applied in treatment.

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Section: Discussionmentioning

confidence: 99%

Identification Hub Genes in Colorectal Cancer by Integrating Weighted Gene Co-Expression Network Analysis and Clinical Validation in vivo and vitro

et al. 2020

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“…Consistent with this, SRC gene copy number in stage IV CRC has been associated with left sided-tumours and liver metastases [ 59 , 60 ]. SFKs upregulation may also involve miRNA epigenetic mechanisms [ 50 ], such as mi-129-1-3p downregulation [ 62 ], and aberrant SFK protein accumulation, that can be induced by inactivation of the ubiquitination factor Casitas B-lineage lymphoma proto-oncogene (Cbl) or inhibition [ 63 ] of Src autophagic degradation through SNX10 inactivation [ 64 ].…”

Section: Sfks In Human Crcmentioning

confidence: 99%

Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis

Sirvent

Mevizou

Naim

et al. 2020

Cancers

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Src, originally identified as an oncogene, is a membrane-anchored tyrosine kinase and the Src family kinase (SFK) prototype. SFKs regulate the signalling induced by a wide range of cell surface receptors leading to epithelial cell growth and adhesion. In the intestine, the SFK members Src, Fyn and Yes regulate epithelial cell proliferation and migration during tissue regeneration and transformation, thus implicating conserved and specific functions. In patients with colon cancer, SFK activity is a marker of poor clinical prognosis and a potent driver of metastasis formation. These tumorigenic activities are linked to SFK capacity to promote the dissemination and tumour-initiating capacities of epithelial tumour cells. However, it is unclear how SFKs promote colon tumour formation and metastatic progression because SFK-encoding genes are unfrequently mutated in human cancer. Here, we review recent findings on SFK signalling during intestinal homeostasis, regeneration and tumorigenesis. We also describe the key nongenetic mechanisms underlying SFK tumour activities in colorectal cancer, and discuss how these mechanisms could be exploited in therapeutic strategies to target SFK signalling in metastatic colon cancer.

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“…The STAT-3 dimer translocates into the nucleus and promotes the transcription of downstream genes. STAT-3, signal transducer and activator of transcription-3; JAK, Janus kinase; c-Myc, MYC proto-oncogene bhLh transcription factor; Bcl-xL, BCL2-like 1; Bcl-2, BCL2 apoptosis regulator; VEGF, vascular endothelial growth factor; PIAS, protein inhibitors of activated STATs; SOCS, suppressors of cytokine signaling.STAT-3 in normal and neoplastic colorectal epithelial cells and tumor tissues with upregulated Src(74). Src homology region 2 domain-containing phosphatase 1 (ShP-1) is a non-receptor protein tyrosine phosphatase and serves as a tumor suppressor gene in numerous cancer types.…”

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confidence: 99%

Overview of the STAT‑3 signaling pathway in cancer and the development of specific inhibitors (Review)

Mohammad

Liu

2020

Oncol Lett

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Signal transducer and activator of transcription (STAT) proteins represent novel therapeutic targets for the treatment of cancer. In particular, STAT-3 serves critical roles in several cellular processes, including the cell cycle, cell proliferation, cellular apoptosis and tumorigenesis. Persistent activation of STAT-3 has been reported in a variety of cancer types, and a poor prognosis of cancer may be associated with the phosphorylation level of STAT-3. Furthermore, elevated STAT-3 activity has been demonstrated in a variety of mammalian cancers, both in vitro and in vivo. This indicates that STAT-3 serves an important role in the progression of numerous cancer types. A significant obstacle in developing STAT-3 inhibitors is the demonstration of the antitumor efficacy in in vivo systems and the lack of animal models for human tumors. Therefore, it is crucial to determine whether available STAT-3 inhibitors are suitable for clinical trials. Moreover, further preclinical studies are necessary to focus on the impact of STAT-3 inhibitors on tumor cells. When considering STAT-3 hyper-activation in human cancer, selective targeting to these proteins holds promise for significant advancement in cancer treatment. In the present study, advances in our knowledge of the structure of STAT-3 protein and its regulatory mechanisms are summarized. Moreover, the STAT-3 signaling pathway and its critical role in malignancy are discussed, in addition to the development of STAT-3 inhibitors in various cancer types. Contents 1. Introduction 2. STAT-3 structure 3. STAT-3 signal transduction cascade 4. Target genes regulated by STAT-3 5. Advances in antitumor therapeutics targeting STAT-3 6. Conclusions

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SNX10 (sorting nexin 10) inhibits colorectal cancer initiation and progression by controlling autophagic degradation of SRC

Cited by 44 publications

References 41 publications

Identification Hub Genes in Colorectal Cancer by Integrating Weighted Gene Co-Expression Network Analysis and Clinical Validation in vivo and vitro

Identification Hub Genes in Colorectal Cancer by Integrating Weighted Gene Co-Expression Network Analysis and Clinical Validation in vivo and vitro

Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis

Overview of the STAT‑3 signaling pathway in cancer and the development of specific inhibitors (Review)

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