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Periostin regulates autophagy through integrin ?5?1 or ?6?4 and an AKT-dependent pathway in colorectal cancer cell migration.

ABSTRACT: Colorectal cancer (CRC) is one of the most fatal cancers with highly invasive properties. The progression of CRC is determined by the driving force of periostin (PN) from cancer-associated fibroblasts (CAFs) in the tumour microenvironment. This present work aims to investigate autophagy-mediated CRC invasion via the receptor integrin (ITG) by PN. The level of PN in 410 clinical CRC tissues was found increased and was an independent poor prognosis marker (HR = 2.578, 95% CI = 1.218-5.457, P-value = .013) with a significant correlation with overall survival time (P-value < .001). PN activated proliferation, migration and invasion of CRC cells, but with reduced autophagy. Interestingly, the reduction of LC3 autophagic protein corresponded to the increased ability of CRC cell migration. The siITG?5-treated HT-29 and siITG?4-treated HCT-116 CRC cells attenuated epithelial-to-mesenchymal transitions (EMT)-related genes and pAKT compared with those in siITG-untreated cells. The reduction of pAKT by a PI3K inhibitor significantly restored autophagy in CRC cells. These evidences confirmed the effect of PN through either ITG?5?1 or ITG?6?4 and the AKT-dependent pathway to control autophagy-regulated cell migration. In conclusion, these results exhibited the impact of PN activation of ITG?5?1 or ITG?6?4 through pAKT in autophagy-mediated EMT and migration in CRC cells.

SUBMITTER: Thongchot S

PROVIDER: S-EPMC7686974 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Periostin regulates autophagy through integrin α5β1 or α6β4 and an AKT-dependent pathway in colorectal cancer cell migration.

Thongchot Suyanee S Singsuksawat Ekapot E Sumransub Nuttavut N Pongpaibul Ananya A Trakarnsanga Attaporn A Thuwajit Peti P Thuwajit Chanitra C

Journal of cellular and molecular medicine 20200929 21

Colorectal cancer (CRC) is one of the most fatal cancers with highly invasive properties. The progression of CRC is determined by the driving force of periostin (PN) from cancer-associated fibroblasts (CAFs) in the tumour microenvironment. This present work aims to investigate autophagy-mediated CRC invasion via the receptor integrin (ITG) by PN. The level of PN in 410 clinical CRC tissues was found increased and was an independent poor prognosis marker (HR = 2.578, 95% CI = 1.218-5.457, P-value ...[more]

PMID: 32990415

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Project description:BackgroundSialic acids are widely distributed in animal tissues, and aberrantly expressed in a variety of cancer types. High expression of sialic acid contributes to tumor aggressiveness by promoting cell proliferation, migration, angiogenesis, and metastasis. Sialidases are responsible for removal of sialic acids from glycoproteins and glycolipids.MethodsN-glycomics of bladder cancer cells were detected by MALDI-TOF mass spectrometry. Sialic acid modification in bladder cancer tissue was determined by lectin blot. The down-regulation of NEU1 in bladder cancer cells was determined by high resolution liquid chromatography mass spectrometry (HR LC-MS). The effects of sialidase NEU1 expression on proliferation and apoptosis of human bladder cancer cells were examined by western blot, RT-PCR, confocal imaging and flow cytometry. Moreover, the function of sialic acids on fibronectin-integrin α5β1 interaction were assayed by immunoprecipitation and ELISA. The importance of NEU1 in tumor formation in vivo was performed using BALB/c-nu mice. Expression of NEU1 in primary human bladder cancer tissue samples was estimated using bladder cancer tissue microarray.Results(1) Downregulation of NEU1 was primarily responsible for aberrant expression of sialic acids in bladder cancer cells. (2) Decreased NEU1 expression was correlated with bladder cancer progression. (3) NEU1 overexpression enhanced apoptosis and reduced proliferation of bladder cancer cells. (4) NEU1 disrupted FN-integrin α5β1 interaction and deactivated the Akt signaling pathway. (5) NEU1 significantly suppressed in vivo tumor formation in BALB/c-nu mice.ConclusionsOur data showed that NEU1 inhibited cancer cell proliferation, induced apoptosis, and suppressed tumor formation both in vitro and in vivo, by disrupting interaction of FN and integrin β1 and inhibiting the Akt signaling pathway. Our observations indicate that NEU1 is an important modulator of the malignant properties of bladder cancer cells, and is a potential therapeutic target for prognosis and treatment of bladder cancer. Video Abstract.

Dataset Information

Periostin regulates autophagy through integrin ?5?1 or ?6?4 and an AKT-dependent pathway in colorectal cancer cell migration.

Publications

Periostin regulates autophagy through integrin α5β1 or α6β4 and an AKT-dependent pathway in colorectal cancer cell migration.

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