Expression and clinical significance of absent in melanoma 2 in colorectal cancer

Zhang, Zhi; Dong, Xiaoqiang; Yang, Xiaodong; Wan, Daiwei; Sun, Liang; Gu, Mengmeng; Li, Ming; Zhu, Zheng; Wang, Jin; Shang, Zhiguo; He, Songbing

doi:10.1016/j.biopha.2017.07.161

Cited by 13 publications

(24 citation statements)

References 29 publications

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“…Colorectal cancer is an important health problem worldwide (22). Despite the development of various diagnostic and treatment strategies, including chemotherapy, the prognosis is poor and the survival rate is low (23). The HER2/AKT/mTOR/S6K1 pathway plays a significant role in CRC.…”

Section: Discussionmentioning

confidence: 99%

Rab1A promotes proliferation and migration abilities via regulation of the HER2/AKT-independent mTOR/S6K1 pathway in colorectal cancer

Cheng

Shao

et al. 2019

Oncol Rep

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Colorectal carcinoma (CRC) is one of the most common malignancies worldwide and the second leading cause of cancer-related deaths in the US. Recently, Rab1A has been reported to be an activator of mTORC1 and p-S6K1, which is downstream of mTORC1. However, the association between Rab1A and p-S6K1 in CRC remains elusive. In the present study, we first demonstrated that Rab1A was overexpressed in CRC tissues and Rab1A overexpression was positively related to lymph node invasion, degree of differentiation, venous invasion and tumor-node-metastasis (TNM) stage. In both TNM stage I–II and III–IV patients, Rab1A-positive patients had a shorter survival time than Rab1A-negative patients. Furthermore, in univariate and multivariate analyses, only Rab1A expression was verified as an independent prognostic factor for survival in CRC patients. The level of p-S6K1 was markedly high in CRC tissues and Rab1A expression level had a positive association with p-S6K1 level. In addition, high levels of both Rab1A and p-S6K1 were associated with a poorer prognosis compared with low expression of either Rab1A or p-S6K1 level. Moreover, high levels of both Rab1A and p-S6K1 were associated with a poorer prognosis than patients with high levels of either Rab1A or p-S6K1 alone. Finally, knockdown of Rab1A expression inhibited migration and proliferation of SW480 and HCT116 cell lines by targeting regulation of p-S6K1. Thus, our findings indicate that Rab1A plays an important role in CRC and may provide a therapeutic target for CRC, particularly for mTORC1-targeted therapy-resistant cancers.

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Section: Discussionmentioning

confidence: 99%

Rab1A promotes proliferation and migration abilities via regulation of the HER2/AKT-independent mTOR/S6K1 pathway in colorectal cancer

Cheng

Shao

et al. 2019

Oncol Rep

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“…21 Despite advancements in treatment strategies, including chemotherapy, the prognosis is still poor. 22 The key challenge in improving CRC prognosis is the molecular heterogeneity of these tumors. 16 Therefore, it is essential to identify novel therapeutic targets in order to improve the survival of CRC patients.…”

Section: Discussionmentioning

confidence: 99%

<p>ENO1 Acts as a Prognostic Biomarker Candidate and Promotes Tumor Growth and Migration Ability Through the Regulation of Rab1A in Colorectal Cancer</p>

Cheng¹,

Shao²,

Xu³

et al. 2019

CMAR

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Background: Colorectal carcinoma (CRC) is one of the most common malignancies with a dismal 5-year survival rate. The glycolytic enzyme α-enolase (ENO1) is overexpressed in multiple cancers and is involved in tumor cell proliferation and metastasis. However, its clinical significance, biological role, and underlying molecular mechanisms in CRC are still unclear. The aim of the present study was to investigate the potential role of ENO1 in the initiation and development of CRC. Patients and methods: The in situ expression of ENO1 in CRC and adjacent normal tissues was examined by immunohistochemistry. The effects of ENO1 on the in vitro proliferation and migration of CRC cell lines were investigated by MTT, colony formation, and Transwell assays. Finally, the in vivo tumorigenic capacity of ENO1 was assessed in a mouse model. Results: ENO1 was overexpressed in CRC tissues and significantly correlated with the clinicopathological parameters. Furthermore, Rab1Awas also overexpressed in CRC tissues and was positively correlated to that of ENO1. The high expression levels of both ENO1 and Rab1A led to significantly worse prognosis of CRC patients compared to either alone. Furthermore, knockdown of ENO1 significantly inhibited CRC cells proliferation and migration in vitro and reduced xenograft growth in vivo via the concomitant downregulation of Rab1A. Conclusion: The ENO1/Rab1A signaling axis is involved in CRC progression and is a potential biomarker for the treatment of CRC.

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“…Liu et al 22 analyzed AIM2 expression at different stages of CRC and found that AIM2 level was significantly lower in stage IV than that in stage I-III. Zhang et al 14 found that AIM2 expression closely related to depth of invasion (high vs F I G U R E 4 Immunofluorescence of the EMT-related proteins in transfected cells. A-C, AIM2 overexpression plasmid transfection was carried out in HCT116, HT-29, and SW620.…”

Section: Discussionmentioning

confidence: 99%

“…5,13 The constitutive expression of AIM2 in human CRC cells shows great differences. 14 We first detected the levels of AIM2 protein and gene in three different human CRC cell lines by Western blot, real-time PCR and immunofluorescence. Compared with the low level of AIM2 in HCT116, AIM2 levels in HT-29 and SW620 were much higher ( Figure 1A-C).…”

Section: Aim2 Affects Migration and Invasion In Crc Cell Linesmentioning

confidence: 99%

Absent in melanoma 2 suppresses epithelial‐mesenchymal transition via Akt and inflammasome pathways in human colorectal cancer cells

Yang

Zhang

Jin

et al. 2019

J of Cellular Biochemistry

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Absent in melanoma 2 (AIM2) is a critical component in natural immunity system and is closely related to cancer initiation and development. It has been shown that AIM2 inhibited colorectal cancer (CRC) development and cell proliferation. It remains unresolved how AIM2 acts on CRC metastasis. In this study, we assessed migration, invasion ability, and epithelial‐mesenchymal transition (EMT) program upon AIM2 overexpression or knockdown in human CRC cells. Transwell assay demonstrated that upregulation of AIM2 reduced cell migration and invasion. Epithelial marker E‐cadherin was augmented and mesenchymal markers vimentin, as well as Snail, were examined decreased by Western blot, real‐time polymerase chain reaction, and immunofluorescence. Correspondingly, knockdown of AIM2 led to a reverse consequence. In addition, AIM2 regulated Akt phosphorylation and effects of AIM2 on cell invasion and EMT were recovered after administration of Akt inhibitor, suggesting that AIM2 suppressed EMT dependent on Akt pathway. In addition, caspase‐1 inhibitor exposure indicated that AIM2 abrogated EMT through the inflammasome pathway as well. In summary, AIM2 suppressed EMT via Akt and inflammasome pathways in human CRC cells.

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Expression and clinical significance of absent in melanoma 2 in colorectal cancer

Cited by 13 publications

References 29 publications

Rab1A promotes proliferation and migration abilities via regulation of the HER2/AKT-independent mTOR/S6K1 pathway in colorectal cancer

Rab1A promotes proliferation and migration abilities via regulation of the HER2/AKT-independent mTOR/S6K1 pathway in colorectal cancer

<p>ENO1 Acts as a Prognostic Biomarker Candidate and Promotes Tumor Growth and Migration Ability Through the Regulation of Rab1A in Colorectal Cancer</p>

Absent in melanoma 2 suppresses epithelial‐mesenchymal transition via Akt and inflammasome pathways in human colorectal cancer cells

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