Decreased HCRP1 promotes breast cancer metastasis by enhancing EGFR phosphorylation

Yang, Wenlin; Wang, Jigang; Wang, Qiangxiu; Qin, Yejun; Lin, Xinhua; Zhou, Danmei; Ren, Kehan; Hou, Changbo; Xu, Jiawen; Liu, Xiuping

doi:10.1016/j.bbrc.2016.06.046

Cited by 14 publications

(11 citation statements)

References 16 publications

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“…Previous studies revealed that loss of chromosome 8p, where VPS37A is located, promotes tumor growth (Cai et al, 2016;Xue et al, 2012). Decreased expression of VPS37 paralogs may be particularly beneficial for cells of advanced stage CRC as RNAi-mediated silencing of VPS37A promoted the resistance of prostate and breast cancer cells to chemotherapeutics (Sun et al, 2017;Yang et al, 2016). Our interrogation of TCGA expression data did not reveal increased transcription of CDKN1A, CDKN2B and CDKN2D in the advanced stages of CRC patients.…”

Section: Discussionmentioning

confidence: 58%

“…Another layer of complexity is added by the incorporation of Vps37 proteins into ESCRT-I to form functionally distinct complexes in the cell (Stefani et al, 2011;Wunderley et al, 2014). Changes in mRNA and protein levels of VPS37A were previously documented in various cancer types, including liver, prostate, breast, ovarian, renal, lung, glioma, gastric, oral and oropharyngeal squamous cell carcinoma and colon cancer (Chen et al, 2015;Chen et al, 2020;Chen et al, 2018;Du et al, 2016;Fu et al, 2018;Lai et al, 2009;Perisanidis et al, 2013;Sun et al, 2017;Vasaikar et al, 2019;Wittinger et al, 2011;Wu et al, 2019;Xu et al, 2017a;Xu et al, 2017b;Xu et al, 2014;Xu et al, 2017c;Xu et al, 2003;Yang et al, 2016;Yang et al, 2017;Zhu et al, 2015). Several of these studies suggested that VPS37A acts as a tumor suppressor and its loss can serve as an adverse prognostic factor.…”

Section: Discussionmentioning

confidence: 96%

“…This notion is consistent with our transcriptomic analysis of CRC cells depleted of Vps37 proteins, which identified processes related to cell migration, growth and signaling. Downregulation of ESCRT-I components was shown in vitro to prolong epidermal growth factor signaling, sensitize cells to low doses of transforming growth factor, as well as promote cell invasion and migration through the process of epithelial to mesenchymal transition (Miller et al, 2018;Yang et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

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Concurrent depletion of Vps37 proteins evokes ESCRT-I destabilization and profound cellular stress responses

Kolmus

Erdenebat

Stewig

et al. 2020

Preprint

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ABSTRACTMolecular details of how endocytosis contributes to oncogenesis remain elusive. Our in silico analysis of colorectal cancer (CRC) patients revealed stage-dependent alterations in the expression of 113 endocytosis-related genes. Among them transcription of the Endosomal Sorting Complex Required for Transport (ESCRT)-I component VPS37B was decreased in the advanced stages of CRC. Expression of other ESCRT-I core subunits remained unchanged in the investigated dataset. We analyzed an independent cohort of CRC patients showing also reduced VPS37A mRNA and protein abundance. Transcriptomic profiling of CRC cells revealed non-redundant functions of Vps37 proteins. Knockdown of VPS37A and VPS37B triggered p21-mediated inhibition of cell proliferation and sterile inflammatory response driven by the Nuclear Factor (NF)-κB transcription factor and associated with mitogen-activated protein kinase signaling. Co-silencing of VPS37C further potentiated activation of these independently induced processes. The type and magnitude of transcriptional alterations correlated with the differential ESCRT-I stability upon individual and concurrent Vps37 depletion. Our study provides novel insights into cancer cell biology by describing cellular stress responses that are associated with ESCRT-I destabilization, which might occur in CRC patients.SUMMARY STATEMENTEndosomal Sorting Complex Required for Transport (ESCRT)-I destabilization upon concurrent depletion of Vps37 proteins is linked to the activation of sterile inflammatory response and cell growth inhibition.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Concurrent depletion of Vps37 proteins evokes ESCRT-I destabilization and profound cellular stress responses

Kolmus

Erdenebat

Stewig

et al. 2020

Preprint

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“…In HCC, downregulation of VPS37A promoted hepatocellular carcinoma cell migration and invasion by induction of EGFR activation and epithelial-mesenchymal transition [ 41 , 42 ]. In breast cancer, VPS37A was downregulated and inhibited breast cancer metastasis through downregulating EGFR phosphorylation [ 43 ]. In this study, we found VPS37A overexpression could significantly inhibit cell proliferation and promote cell apoptosis in PCa cells.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-19a acts as a prognostic marker and promotes prostate cancer progression via inhibiting VPS37A expression

Wang

Kong

et al. 2017

Oncotarget

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Prostate cancer (PCa) is a leading cause of cancer-related deaths among males worldwide. However, the molecular mechanisms underlying the progression of PCa remain unclear. Despite several reported miRNAs in prostate cancer, these reports lacked system-level identification of differentially expressed miRNAs in large sample size. Moreover, it's still largely unknown how miRNAs result in tumorigenesis and progression of PCa. Therefore, by analyzing three public databases, we identified 16 upregulated miRNAs and 13 downregulated miRNAs, and validated miR-19a was one of the most upregulated miRNAs using qRT-PCR. The dual-luciferase reporter assays indicated VPS37A was a potential target of miR-19a. Functional assays revealed miR-19a served as an oncogene by inhibiting VPS37A. Notably, a significant inverse correlation of miR-19a and VPS37A expression was observed in PCa specimens. Moreover, miR-19a-high and VPS37A-low phenotypes were associated with poor prognosis with biochemical recurrence-free probability. In this study, we confirmed the oncogenic role of miR-19a via targeting VPS37A in PCa, identifying miR-19a and VPS37A as diagnosis and therapeutic biomarkers for PCa.

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“…HCRP1 was first described as a growth inhibitory protein in HCC cells (5). Thereafter, additional physiologic functions of HCRP1 were explored in other tumors such as ovarian, oral and oropharyngeal, breast, and non-small cell lung cancer (6)(7)(8)(9)(10). HCRP1 is a member of the endosomal sorting complex required for transport (ESCRT)-Ι complex and affects lysosomal sorting of EGFR (11).…”

Section: Introductionmentioning

confidence: 99%

HCRP1 inhibits TGF-β induced epithelial-mesenchymal transition in hepatocellular carcinoma

Yang

Wang

et al. 2017

International Journal of Oncology

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Hepatocellular carcinoma-related protein 1 (HCRP1), also known as human vacuolar protein sorting 37 homologue A (hVps37A), has not been detected or is significantly downregulated in hepatocellular carcinoma (HCC) tissues. However, information on the regulatory mechanisms of HCRP1 in HCC remains unclear. Here we found that the downregulation of HCRP1 in HepG2 cells (with low invasion capacity) significantly enhanced migration and invasion, whereas HCRP1 upregulation in SMMC-7721 cells (with high invasion capacity) generated the opposite result. Interestingly, the morphology of HepG2 cells significantly changed from an epithelial to mesenchymal phenotype after HCRP1 knockdown. Moreover, we observed a decrease in the expression of epithelial cell markers E-cadherin and β-catenin, and an increase in the expression of mesenchymal cell markers N-cadherin and vimentin. We also observed that the downregulation of HCRP1 induced epithelial-mesenchymal transition (EMT) through the transforming growth factor-β pathway. Together, our findings define a novel function for HCRP1 from the perspective of EMT, which is closely associated with the migration and invasion of HCC cells.

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Decreased HCRP1 promotes breast cancer metastasis by enhancing EGFR phosphorylation

Cited by 14 publications

References 16 publications

Concurrent depletion of Vps37 proteins evokes ESCRT-I destabilization and profound cellular stress responses

Concurrent depletion of Vps37 proteins evokes ESCRT-I destabilization and profound cellular stress responses

MicroRNA-19a acts as a prognostic marker and promotes prostate cancer progression via inhibiting VPS37A expression

HCRP1 inhibits TGF-β induced epithelial-mesenchymal transition in hepatocellular carcinoma

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