Overexpression of sortilin is associated with 5‐FU resistance and poor prognosis in colorectal cancer

Blondy, Sabrina; Talbot, Hugo; Saada, Sofiane; Christou, Niki; Battu, Serge; Pannequin, Julie; Jauberteau, Marie‐Odile; Lalloué, Fabrice; Verdier, Mireille; Mathonnet, Muriel; Perraud, Aurélie

doi:10.1111/jcmm.15752

Cited by 16 publications

(14 citation statements)

References 57 publications

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“…According to earlier studies, patients with higher or positive SORT1 expression exhibited worse prognosis and advanced tumor progression in breast cancer, 14 B acute lymphoblastic leukemia, 27 neuroendocrine tumors 16 and colorectal cancer, 13 suggesting that SORT1 could be a biomarker to predict the survival time of patients with malignant tumors. In this research, after data mining based on the TCGA-LIHC dataset, it was uncovered that SORT1 expression was substantially As demonstrated in previous studies, SORT1 inhibition could slow down tumor growth and cancer progression.…”

Section: Discussionmentioning

confidence: 99%

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Sortilin 1 regulates hepatocellular carcinoma progression by activating the PI3K/AKT signaling

Wang

Zhou

et al. 2022

Hum Exp Toxicol

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Background Sortilin 1 (SORT1) has been reported as an oncogene in several human tumors. Nonetheless, the biological functions of SORT1 in hepatocellular carcinoma (HCC) remain poorly understood. Methods Western blotting was employed for the determination of protein expression. Hepatocellular carcinoma cell viability, apoptosis, migration, and invasion were measured via CCK-8, flow cytometry, wound healing, and Transwell assays. Results Sortilin 1 was upregulated in HCC and closely associated with unsatisfactory outcomes of HCC patients. Furthermore, in vitro and in vivo assays revealed that SORT1 knockdown significantly diminished HCC cell proliferation and metastasis but accelerated HCC cell apoptosis; moreover, SORT1 depletion also restrained the growth of xenografted HCC tumors. Mechanistically, SORT1 activated PI3K/AKT signaling in HCC cells, thereby promoting the malignant behaviors of HCC cells. Conclusion This study demonstrated that SORT1 might promote HCC progression by activating PI3K/AKT signaling, indicating that SORT1 might be a promising target and biomarker for HCC treatment and prognosis.

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Section: Discussionmentioning

confidence: 99%

“…12 As a multifaceted protein, SORT1 assumes cancerogenic or anticancer roles in human cancers depending on the origin of the tumors. 13 For instance, SORT1 silencing retards breast cancer progression and lung metastases. 14 Sortilin 1 knockdown suppresses gastric cancer cell proliferation, invasion, and migration.…”

Section: Introductionmentioning

confidence: 99%

Sortilin 1 regulates hepatocellular carcinoma progression by activating the PI3K/AKT signaling

Wang

Zhou

et al. 2022

Hum Exp Toxicol

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“…In our study, we screened HCC genes from GEO and TCGA data and identi ed the di erentially expressed molecule Sort1 from the di erential genes. Previous studies have shown that Sort1 acts as an oncogene that is linked with poor prognosis in gastric [24], prostate [25], and colorectal cancers [26], but there is no relevant study on a similar mechanism in HCC. We veri ed the ability of reduced Sort1 expression in inhibiting HCC proliferation and invasion, with the ndings expected to re ect the potential importance of using Sort1 to assess the prognosis of HCC.…”

Section: Discussionmentioning

confidence: 99%

Sortilin 1 Promotes Hepatocellular Carcinoma Cell Proliferation and Migration by Regulating Immune Cell Infiltration

Gao

Song

et al. 2022

Journal of Oncology

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Objectives. Recent evidence suggests that Sort1 promotes carcinogenesis and tumor progression in multiple types of cancers. This study investigates the role of Sort1 in hepatocellular carcinoma (HCC). Methods. The differentially expressed gene was screened through GEO and TCGA databases. The Sort1 gene was identified and its expression was then verified by TCGA and HCCDB (a database of hepatocellular carcinoma expression atlas) databases. The Human Protein Atlas database was used to assess the gene expression in tissues. The TCGA and KM-plotter databases were used to study the relationship between Sort1 and HCC. The correlation between Sort1 and immune cells was evaluated through the TIMER database. GO and KEGG enrichment analysis was used to investigate the possible mechanism. The role of Sort1 in cell proliferation and invasion of HCC was further explored through in vitro experiments. Result. The differentially expressed molecule obtained from database screening was Sort1. Its expression was higher in cancer tissues than in paracancerous ones, and it was mainly located in the cytoplasm. The TCGA, KM-plotter databases, and our study data showed that low expression of Sort1 in HCC patients had better overall survival (OS), progression-free survival (PFI), and disease-specific survival (DSS). Further analysis indicated a significant correlation between Sort1 expression and immune cell infiltration. The gene set enrichment analysis (GSEA) analysis showed that Sort1 affected the biological events of HCC by participating in the WNT, TGF-BETA, JAK, STAT, and CALCIUM signaling pathways. In vitro, cytological experiments demonstrated reduced expression of PCNA, Ki-67, Vimentin, N-cadherin, and MMP-9 mRNA after knocking down Sort1, although E-cadherin expression was promoted. Overall, these processes reduced the ability of proliferation and invasion of HCC cells. Conclusion. Downregulation of Sort1 can prolong the OS, PFI, and DSS of HCC patients. Furthermore, due to its link with immune cell infiltration, the Sort1 gene represents a potentially novel predictive biomarker of HCC. The growth of HCC can be significantly inhibited by interfering with Sort1; therefore, these results provide a potential target for developing anticancer strategies for HCC.

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“…Focusing on cancers, and particularly on colorectal cancers, most studies on the role of Sortilin/NTSR3 have been performed on in vitro models (human colorectal cancer cell lines). A recent study carried out on both cell lines and primary cultures from patients demonstrated that the overexpression of Sortilin/NTSR3 was associated with 5-fluorouracil (5-FU) resistance and a poor prognosis in colorectal cancer [ 85 ].…”

Section: Discussionmentioning

confidence: 99%

Deciphering Mechanisms of Action of Sortilin/Neurotensin Receptor-3 in the Proliferation Regulation of Colorectal and Other Cancers

Mazella

2022

IJMS

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The purpose of this review is to decipher the mechanisms of the pathways leading to the complex roles of neurotensin (NTS) receptor-3, also called sortilin, and of its soluble counterpart (sSortilin/NTSR3) in a large amount of physiological and pathological functions, particularly in cancer progression and metastasis. Sortilin/NTSR3 belongs to the family of type I transmembrane proteins that can be shed to release its extracellular domain from all the cells expressing the protein. Since its discovery, extensive investigations into the role of both forms of Sortilin/NTSR3 (membrane-bound and soluble form) have demonstrated their involvement in many pathophysiological processes from cancer development to cardiovascular diseases, Alzheimer’s disease, diabetes, and major depression. This review focuses particularly on the implication of membrane-bound and soluble Sortilin/NTSR3 in colorectal cancer tissues and cells depending on its ability to be associated either to neurotrophins (NTs) or to NTS receptors, as well as to other cellular components such as integrins. At the end of the review, some hypotheses are suggested to counteract the deleterious effects of these proteins in order to develop effective anti-cancer treatments.

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Overexpression of sortilin is associated with 5‐FU resistance and poor prognosis in colorectal cancer

Cited by 16 publications

References 57 publications

Sortilin 1 regulates hepatocellular carcinoma progression by activating the PI3K/AKT signaling

Sortilin 1 regulates hepatocellular carcinoma progression by activating the PI3K/AKT signaling

Sortilin 1 Promotes Hepatocellular Carcinoma Cell Proliferation and Migration by Regulating Immune Cell Infiltration

Deciphering Mechanisms of Action of Sortilin/Neurotensin Receptor-3 in the Proliferation Regulation of Colorectal and Other Cancers

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