LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor

Ji, Yibing; Kumar, Rahul; Gokhale, Abhiram; Chao, Hseu-Ping; Rycaj, Kiera; Chen, Xin; Li, Qiuhui; Tang, Dean G.

doi:10.1016/j.semcancer.2020.12.016

Cited by 15 publications

(15 citation statements)

References 115 publications

(223 reference statements)

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“…Since 2002, our lab has been studying PCa from the perspective of deregulated organ differentiation by systematically and meticulously dissecting phenotypic and functional properties of heterogeneous PCa cell populations and studying molecular regulators in HPCa samples, PDX, xenografts and cell cultures [ 2 , 3 , 16 – 18 , 20 , 117 – 169 ] ( Figs. 2 – 13 ).…”

Section: Introductionmentioning

confidence: 99%

“…Our studies on PCa cell subpopulations and their molecular regulation [ 117 – 169 ] in multiple xenograft and PDX models as well as > 200 patient tumors and tumor-derived cells and organoids (e.g., Figs. 2 , 4 , 7 , 8 ) suggest that human PCSCs that meet at least some of the CSC definitions [ 3 , 120 , 129 , 140 , 145 , 160 ] are phenotypically heterogeneous.…”

Section: Introductionmentioning

confidence: 99%

“…Studying the genetic, transcriptomic and cellular heterogeneity in PCa [ 2 , 80 – 116 , 325 ] and in-depth elucidation of PCSCs [ 117 – 169 , 218 – 324 ] have direct relevance to understanding the mechanisms of therapy resistance [ 326 , 327 ]. Recent studies in PCa patients undergoing neoadjuvant ADT trials have directly linked the clonal heterogeneity, i. e., ITH, to distinct clinical responses [ 328 – 330 ].…”

Section: Introductionmentioning

confidence: 99%

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Understanding and targeting prostate cancer cell heterogeneity and plasticity

Tang¹

2022

Seminars in Cancer Biology

Self Cite

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Understanding and targeting prostate cancer cell heterogeneity and plasticity

Tang¹

2022

Seminars in Cancer Biology

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“…Lrig1 has evolved as a tumour suppressor, which is feedback-induced by multiple oncogenic signals shown both in vitro and in vivo [ 24 , 25 , 26 ]. In vivo, Lrig1 controls proliferation by modulating the amplitude of ErbB signalling in proliferative Lrig1+ stem cells [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

HPV8 Reverses the Transcriptional Output in Lrig1 Positive Cells to Drive Skin Tumorigenesis

Syed

Marcuzzi

Miller-Lazic

et al. 2022

Cancers

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K14-HPV8-CER transgenic mice express the complete early genome region of human papillomavirus type 8 (HPV8) and develop skin tumours attributed to the expansion of the Lrig1+ stem cell population. The correlation between HPV8-induced changes in transcriptional output in the stem cell compartment remains poorly understood. To further understand the oncogenic pathways underlying skin tumour formation we examined the gene expression network in skin tumours of K14-HPV8-CER mice and compared the differentially expressed genes (DEG) with those of the Lrig1-EGFP-ires-CreERT2 mice. Here, we report 397 DEGs in skin tumours of K14-HPV8-CER mice, of which 181 genes were up- and 216 were down-regulated. Gene ontology and KEGG pathway enrichment analyses suggest that the 397 DEGs are acting in signalling pathways known to be involved in skin homeostasis. Interestingly, we found that HPV8 early gene expression subverts the expression pattern of 23 cellular genes known to be expressed in Lrig1+ keratinocytes. Furthermore, we identified putative upstream regulating transcription factors as well as miRNAs in the control of these genes. These data provide strong evidence that HPV8 mediated transcriptional changes may contribute to skin tumorigenesis, offering new insights into the mechanism of HPV8 driven oncogenesis.

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“…LRIG1 was identified more than 20 years prior. LRIG1 was found to be downregulated or absent in many carcinomas and acts as a tumor suppressor (23). For example, in prostate cancer, malignant glioma, and other cancers, LRIG1 acts as a tumor suppressor (24,25).…”

Section: Introductionmentioning

confidence: 99%

hsa_circ_0000006 induces tumorigenesis through miR-361- 3p targeting immunoglobulin-like domains protein 1 (LRIG1) in osteosarcoma

Gao

Liu²,

Zhao

et al. 2021

Ann Transl Med

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Background: Osteosarcoma (OS) is considered to be the most highly prevalent bone tumor. In the progression of different human cancers, the role of circular RNAs (circRNAs) has been extensively studied.Microarray analysis has indicated that hsa_circ_0000006 expression was lower in OS, but the mechanism of hsa_circ_0000006 in regulating the progression of OS remains elusive.Methods: The expression of cancer-related genes at the transcriptional and translational levels was assessed by RT-qPCR and western blotting (WB). Colony formation and Cell Counting Kit-8 (CCK-8) assays were used to evaluate the proliferative potential of cells. The transwell assay was used to examine the invasive and migratory potential of cells. Furthermore, dual-luciferase reporter (DLR) and RNA pull-down assays were performed for the validation of the targeting sites of hsa_circ_0000006, miR-361-3p, and the 3'-untranslated region (3'-UTR) of immunoglobulin-like domains protein 1 (LRIG1) mRNA. Moreover, the protein levels of epithelial-to-mesenchymal transition (EMT) markers were analyzed by WB.Results: The expression of hsa_circ_0000006 and LRIG1 were found to be down-regulated in OS tissues and cells, while miR-361-3p was up-regulated. Knockdown of hsa_circ_0000006 promoted the progression and development of OS, as well as EMT. Furthermore, hsa_circ_0000006 was revealed as a sponge of miR-361-3p, which negatively regulates miR-361-3p expression. LRIG1 was found to be an miR-361-3p target.In OS cells, the LRIG1 expression level was decreased, with elevated expression of miR-361-3p. Advanced studies demonstrated that hsa_circ_0000006 regulates LRIG1 expression through sponging miR-361-3p, then promotes the tumorigenesis of OS.Conclusions: hsa_circ_0000006 is associated with the progression and development of OS through miR-361-3p by target LRIG1, which is a significant biomarker and effective therapeutic target for patients with OS.

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LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor

Cited by 15 publications

References 115 publications

Understanding and targeting prostate cancer cell heterogeneity and plasticity

Understanding and targeting prostate cancer cell heterogeneity and plasticity

HPV8 Reverses the Transcriptional Output in Lrig1 Positive Cells to Drive Skin Tumorigenesis

hsa_circ_0000006 induces tumorigenesis through miR-361- 3p targeting immunoglobulin-like domains protein 1 (LRIG1) in osteosarcoma

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