Formin-like 3 regulates RhoC/FAK pathway and actin assembly to promote cell invasion in colorectal carcinoma

Zeng, Yuanfeng; Xiao, Yuchen; Liu, Yong; Luo, Xugang; Wen, Li-Dan; Liu, Qian; Chen, Min

doi:10.3748/wjg.v24.i34.3884

Cited by 26 publications

(18 citation statements)

References 53 publications

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“…Further analysis revealed that increased HOXD10 led to suppression of the MAPK and AKT pathways known to regulate RhoC [68]. The interaction of FMNL-3 with RhoC was seen to lead to increased MMP2, MMP9 and VEGF, consequently leading to increased invasion in colon cancer cell lines [69]. The knockdown of RhoC in cholangiocellular carcinoma cells on the other hand, resulted in the suppression of invasion and migration [70].…”

Section: Introductionmentioning

confidence: 99%

RhoC: a fascinating journey from a cytoskeletal organizer to a Cancer stem cell therapeutic target

Thomas

Pranatharthi

Ross

et al. 2019

J Exp Clin Cancer Res

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Tumor heterogeneity results in differential response to therapy due to the existence of plastic tumor cells, called cancer stem cells (CSCs), which exhibit the property of resistance to therapy, invasion and metastasis. These cells have a distinct, signaling network active at every stage of progression. It is difficult to envisage that the CSCs will have a unique set of signaling pathways regulating every stage of disease progression. Rather, it would be easier to believe that a single pivotal pathway having significant contribution at every stage, which can further turn on a battery of signaling mechanisms specific to that stage, would be instrumental in regulating the signaling network, enabling easy transition from one state to another. In this context, we discuss the role of RhoC which has contributed to several phenotypes during tumor progression. RhoC (Ras homolog gene family member C) has been widely reported to regulate actin organization. It has been shown to impact the motility of cancer cells, resultantly affecting invasion and metastasis, and has contributed to carcinoma progression of the breast, pancreas, lung, ovaries and cervix, among several others. The most interesting finding has been its indispensable role in metastasis. Also, it has the ability to modulate various other phenotypes like angiogenesis, motility, invasion, metastasis, and anoikis resistance. These observations suggest that RhoC imparts the plasticity required by tumor cells to exhibit such diverse functions based on microenvironmental cues. This was further confirmed by recent reports which show that it regulates cancer stem cells in breast, ovary and head and neck cancers. Studies also suggest that the inhibition of RhoC results in abolition of advanced tumor phenotypes. Our review throws light on how RhoC, which is capable of modulating various phenotypes may be the apt core signaling candidate regulating disease progression. Additionally, mice studies show that RhoC is not essential for embryogenesis, giving scope for its development as a possible therapeutic target. This review thus stresses on the need to understand the protein and its functioning in greater detail to enable its development as a stem cell marker and a possible therapeutic target .

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Section: Introductionmentioning

confidence: 99%

RhoC: a fascinating journey from a cytoskeletal organizer to a Cancer stem cell therapeutic target

Thomas

Pranatharthi

Ross

et al. 2019

J Exp Clin Cancer Res

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“…Additionally, FMNL2 has been regarded as a potential target for abnormal proliferation in colorectal cancer [ 25 , 26 ]. FMNL1 increases the proliferation of leukemia cells [ 27 ], and FMNL3 promotes cell proliferation and clonogenicity in colorectal cancer [ 28 ]. However, the function of FMNL2 in breast cancer cell proliferation has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Formin-like protein 2 promotes cell proliferation by a p27-related mechanism in human breast cancer cells

Jiao

Wang

Chen³

et al. 2021

BMC Cancer

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Background Breast cancer is the leading cause of cancer-related deaths in females worldwide. Formin-like protein 2 (FMNL2) is a member of formin family that governs cytokinesis, cell polarity, morphogenesis and cell division. To our knowledge, the function of FMNL2 in breast cancer proliferation still remains uncovered. Methods Tumor immune estimation resource (TIMER) analysis was used to detect the correlation between FMNL2 and Ki67 in breast cancer tissues. Quantitative real-time transcription polymerase chain reaction (qRT-PCR) and western blotting were performed to analyze the expression in human breast cancer cells. Moreover, RNA interference (RNAi) and plasmids were performed to silence and overexpress FMNL2 and p27. The CCK8, MTT, cell counting, colony formation, and 5-ethynyl-2-deoxyuridine (EdU) incorporation assays were used to detect cell proliferation, respectively. Flow cytometry analysis was used to detect cell cycle distribution. Further, the distribution of p27 was examined using immunofluorescence. Results We found that FMNL2 expression was positively associated with Ki67 among collected breast cancer tissues and in TCGA database. Compared to lower proliferative cells MCF7 and T47D, FMNL2 was overexpressed in highly proliferative breast cancer cells MDA-MB-231, BT549 and SUM159, accompanied by reduced levels of p27 and p21, and elevated CyclinD1 and Ki67 expression. FMNL2 silencing significantly inhibited the cell proliferation of MDA-MB-231 and BT549 cells. Meanwhile, FMNL2 overexpression distinctly promoted the cell proliferation of MCF7 cells. Furthermore, FMNL2 suppressed the nuclear levels of p27 and promoted p27 proteasomal degradation in human breast cancer cells. The ubiquitination of p27 was inhibited by FMNL2 silencing in BT549 cells. Besides, p27 silencing markedly elevated Ki67 expression and cell viability, which could be blocked by additionally FMNL2 silencing in MDA-MB-231 and BT549 cells. Furthermore, overexpression of p27WT significantly reversed the increased levels of FMNL2 and Ki67, cell viability and cell cycle progression induced by FMNL2 overexpression in MCF7 cells. More importantly, compared to p27WT group, those effects could be significantly reversed by p27△NLS overexpression. Conclusions These results demonstrated that FMNL2 promoted cell proliferation partially by reducing p27 nuclear localization and p27 protein stability in human breast cancer cells, suggesting the pivotal role of FMNL2 in breast cancer progression.

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“…C/EBPs are a family of transcription factors including CEBPG that regulate growth and differentiation of various tissues and control redox homeostasis in normal and cancerous cells [ 33 34 ]. FMNL3 is an oncogene in tongue squamous cell carcinoma, nasopharyngeal carcinoma, and colorectal carcinoma [ 35 36 ]. This study found that circFoxp1 positively regulated the expression of CEBPG and FMNL3 through miR-22 and miR-150-3p, suggesting that CEBPG and FMNL3 are oncogenes in ovarian cancer, but the specific regulatory mechanism still needs more experimental proof.…”

Section: Discussionmentioning

confidence: 99%

Circulating exosomal circFoxp1 confers cisplatin resistance in epithelial ovarian cancer cells

Luo

Gui

2020

J Gynecol Oncol

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Objective: Early detection and treatment are particularly important to epithelial ovarian cancer (EOC). Studies have shown that circular RNA (circRNA) dysregulation is associated with the proliferation and metastasis of ovarian cancer cells. This study focused on the role of serum exosomal circular forkhead box protein P1 (circFoxp1) on survival outcome and cisplatin (DDP) resistance in patients with EOC. Methods: Quantitative polymerase chain reaction, 5-ethynyl-2′-deoxyuridine (EdU) staining, CCK-8, luciferase reporter assay, RNA immunoprecipitation, tumor xenograft in nude mice, and bioinformatic analysis were performed. Results: Circulating exosomal circFoxp1 was significantly increased in patients with EOC, especially in DDP-resistant EOC patients. circFoxp1 expression was positively associated with International Federation of Gynecology and Obstetrics stage, primary tumor size, lymphatic metastasis, distant metastasis, residual tumor diameter, and clinical response. Exosomal circFoxp1 also was an independent factor predicting survival and disease recurrence in patients with EOC. Overexpression of circFoxp1 could promote cell proliferation and confer DDP resistance, while knockdown of circFoxp1 could inhibit cell proliferation and enhance DDP sensitivity in vitro and in vivo. In addition, miR-22 and miR-150-3p mimic treatment attenuated circFoxp1-meadiated DDP resistance, while miR-22 and miR-150-3p inhibitor treatment enhanced DDP resistance that mitigated by circFoxp1 knockdown. Furthermore, circFoxp1 positively regulated the expression of CCAAT enhancer binding protein gamma (CEBPG) and formin like 3 (FMNL3) through miR-22 and miR-150-3p. Conclusions: circFoxp1 is an oncogene in EOC cells and can confer DDP resistance to EOC cells. Circulating exosomal circFoxp1 can be used as a biomarker and potential therapeutic target for EOC.

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Formin-like 3 regulates RhoC/FAK pathway and actin assembly to promote cell invasion in colorectal carcinoma

Cited by 26 publications

References 53 publications

RhoC: a fascinating journey from a cytoskeletal organizer to a Cancer stem cell therapeutic target

RhoC: a fascinating journey from a cytoskeletal organizer to a Cancer stem cell therapeutic target

Formin-like protein 2 promotes cell proliferation by a p27-related mechanism in human breast cancer cells

Circulating exosomal circFoxp1 confers cisplatin resistance in epithelial ovarian cancer cells

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