Filamin A interacting protein 1-like expression inhibits progression in colorectal cancer

Park, Young‐Lan; Park, Sunyoung; Lee, Seung–Hyun; Kim, Rul-Bin; Kim, Joong-Keun; Rew, Sung-Yoon; Myung, Dae‐Seong; Cho, Sung-Bum; Lee, Wan‐Sik; Kim, Hyunsoo; Joo, Young‐Eun

doi:10.18632/oncotarget.12664

Cited by 15 publications

(16 citation statements)

References 32 publications

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“…A previous study showed that there is a positive relationship between FLNa and VEGF in patients with lung cancer (43). However, a separate study emphasized that FLNa interacting with other proteins inhibits CRC progression (44), indicating that FLNa may represent a novel cancer-suppressor gene for treating colorectal adenocarcinoma. Thus, the current literature suggests a dual role for FLNa and complex underlying mechanisms in various types of cancer.…”

Section: Discussionmentioning

confidence: 99%

Filamin A regulates EGFR/ERK/Akt signaling and�affects colorectal cancer cell growth and migration

Wang

Zhu

2019

Mol Med Report

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The metastasis and recurrence rate, and the overall prognosis of colorectal cancer (CRC) remain unsatisfactory. Filamin A (FLNa), as an actin-binding protein, can interact with various signaling molecules and membrane receptors to affect cell signal transduction and function. However, whether FLNa is involved in the progression of CRC remains to be elucidated. The aim of the present study was to explore the role of FLNa in CRC cell proliferation and migration, as well as in the regulation of epidermal growth factor receptor (EGFR) signaling. Following transfection with a FLNa-targeting short hairpin RNA plasmid to knockdown expression of FLNa in the EGF-treated SW480 cell line, it was found that decreased expression of FLNa promoted cell proliferation and migration. Additionally, there was a negative correlation between FLNa levels and the activation of EGFR and Akt signaling pathways. Similarly, the expression of FLNa was significantly lower in human CRC tissues compared with adjacent normal tissues and FLNa expression was negatively correlated with the expression of Ki-67 in human CRC tissues. Although there was no significant difference in the Kaplan-Meier estimate of CRC between high expression and low expression of FLNa, there were significant negative associations between FLNa expression and TNM stage. The results suggested that FLNa may participate in EGF-induced cell proliferation and migration in CRC cells. Hence, interventions in the FLNa-mediated signaling pathway could provide attractive therapeutic targets for CRC.

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Section: Discussionmentioning

confidence: 99%

Filamin A regulates EGFR/ERK/Akt signaling and�affects colorectal cancer cell growth and migration

Wang

Zhu

2019

Mol Med Report

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“…Additionally, FILIP1L has been shown to have a role in inhibition of WNT signaling pathway, a pathway implicated in colorectal cancer and metastasis as well as in cellular invasion in an ovarian cancer model and colon cancer cell lines . Consistent with these results, another study showed that reduced levels of this protein in colorectal tumors were associated with reduced overall survival times of patients . While it is currently unknown whether these INDELs/CNVs have biological effects on the corresponding genes (and hence, have direct effects on the disease progression and risk of relapse in colorectal cancer), it is quite possible as a large number of noncoding sequences in the human genome contain regulatory elements .…”

Section: Discussionmentioning

confidence: 70%

Germline INDELs and CNVs in a cohort of colorectal cancer patients: their characteristics, associations with relapse‐free survival time, and potential time‐varying effects on the risk of relapse

Werdyani

Skardasi

et al. 2017

Cancer Medicine

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INDELs and CNVs are structural variations that may play roles in cancer susceptibility and patient outcomes. Our objectives were a) to computationally detect and examine the genome-wide INDEL/CNV profiles in a cohort of colorectal cancer patients, and b) to examine the associations of frequent INDELs/CNVs with relapse-free survival time. We also identified unique variants in 13 Familial Colorectal Cancer Type X (FCCX) cases. The study cohort consisted of 495 colorectal cancer patients. QuantiSNP and PennCNV algorithms were utilized to predict the INDELs/CNVs using genome-wide signal intensity data. Duplex PCR was used to validate predictions for 10 variants. Multivariable Cox regression models were used to test the associations of 106 common variants with relapse-free survival time. Score test and the multivariable Cox proportional hazards models with time-varying coefficients were applied to identify the variants with time-varying effects on the relapse-free survival time. A total of 3486 distinct INDELs/CNVs were identified in the patient cohort. The majority of these variants were rare (83%) and deletion variants (81%). The results of the computational predictions and duplex PCR results were highly concordant (93-100%). We identified four promising variants significantly associated with relapse-free survival time (P < 0.05) in the multivariable Cox proportional hazards regression models after adjustment for clinical factors. More importantly, two additional variants were identified to have time-varying effects on the risk of relapse. Finally, 58 rare variants were identified unique to the FCCX cases; none of them were detected in more than one patient. This is one of the first genome-wide analyses that identified the germline INDEL/CNV profiles in colorectal cancer patients. Our analyses identified novel variants and genes that can biologically affect the risk of relapse in colorectal cancer patients. Additionally, for the first time, we identified germline variants that can potentially be earlyrelapse markers in colorectal cancer. Cancer Medicine Open Access 1221

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“…In addition, Filamin A interacting protein 1-like (FILIP1L), which was reported to be down-regulated in EOC and negatively correlated with EOC tumor stages, chemoresistance, and patient survival [69], has been found to induce β-catenin degradation [69, 72]. While the underlying mechanism by which FILIP1L inhibits β-catenin has not been determined in EOC, knockdown of FILIP1L in colon cancer cell lines led to an increase in phosphorylated AKT and GSK-3β and a decrease in phosphorylated β-catenin levels, suggesting that FILIP1L may promote β-catenin degradation by inhibiting AKT and thereby increasing GSK3β activity [73]. Finally, RAB14, a member of the RAS small G-protein superfamily [68, 74], has also been reported to be upregulated in EOC tissues and cell lines [68].…”

Section: Introductionmentioning

confidence: 99%

Wnt/β-catenin signalling in ovarian cancer: Insights into its hyperactivation and function in tumorigenesis

et al. 2019

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Epithelial ovarian cancer (EOC) is the deadliest female malignancy. The Wnt/β-catenin pathway plays critical roles in regulating embryonic development and physiological processes. This pathway is tightly regulated to ensure its proper activity. In the absence of Wnt ligands, β-catenin is degraded by a destruction complex. When the pathway is stimulated by a Wnt ligand, β-catenin dissociates from the destruction complex and translocates into the nucleus where it interacts with TCF/LEF transcription factors to regulate target gene expression. Aberrant activation of this pathway, which leads to the hyperactivity of β-catenin, has been reported in ovarian cancer. Specifically, mutations of CTNNB1, AXIN, or APC, have been observed in the endometrioid and mucinous subtypes of EOC. In addition, upregulation of the ligands, abnormal activation of the receptors or intracellular mediators, disruption of the βcatenin destruction complex, inhibition of the association of β-catenin/E-cadherin on the cell membrane, and aberrant promotion of the β-catenin/TCF transcriptional activity, have all been reported in EOC, especially in the high grade serous subtype. Furthermore, several non-coding RNAs have been shown to regulate EOC development, in part, through the modulation of Wnt/β-catenin signalling. The Wnt/β-catenin pathway has been reported to promote cancer stem cell self-renewal, metastasis, and chemoresistance in all subtypes of EOC. Emerging evidence also suggests that the pathway induces ovarian tumor angiogenesis and immune evasion. Taken together, these studies demonstrate that the Wnt/β-catenin pathway plays critical roles in EOC development and is a strong candidate for the development of targeted therapies.

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Filamin A interacting protein 1-like expression inhibits progression in colorectal cancer

Cited by 15 publications

References 32 publications

Filamin A regulates EGFR/ERK/Akt signaling and�affects colorectal cancer cell growth and migration

Filamin A regulates EGFR/ERK/Akt signaling and�affects colorectal cancer cell growth and migration

Germline INDELs and CNVs in a cohort of colorectal cancer patients: their characteristics, associations with relapse‐free survival time, and potential time‐varying effects on the risk of relapse

Wnt/β-catenin signalling in ovarian cancer: Insights into its hyperactivation and function in tumorigenesis

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