Understanding the routes of metastasis in colorectal cancer

Leake, Isobel

doi:10.1038/nrgastro.2014.60

Cited by 18 publications

(15 citation statements)

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“…CRC cells undergo a series of pathologic events during the metastatic process, including invading deep into the intestinal wall, entering into the circulatory or lymphovascular system, arresting at a remote site, proliferation and induction of angiogenesis [ 36 ]. Certainly, lymph node and distant metastasis in CRC patients is a negative prognostic factor [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Neuron navigator 2 overexpression indicates poor prognosis of colorectal cancer and promotes invasion through the SSH1L/cofilin-1 pathway

Tan¹,

Zhu²,

Tao³

et al. 2015

J Exp Clin Cancer Res

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BackgroundNeuron navigator 2 (NAV2) encodes a member of the neuron navigator gene family, which plays a role in tumorigenesis and cell migration. However, the prognostic value of NAV2 expression in colorectal cancer (CRC) patients and the potential pathway through which NAV2 promotes migration and invasion in CRC cell lines is poorly understood.MethodsThe expression level of NAV2 was detected in CRC tissues from two different CRC cohorts by immunohistochemistry, qRT-PCR and Western blotting; the correlation between NAV2 expression and clinicopathological characters was analyzed, and the prognostic value of NAV2 expression was analyzed using a Cox regression model. CRC cell lines with NAV2 knocked out were used to validate the function and potential pathway used by NAV2 to promote CRC cell migration and invasion.ResultsThe results showed that NAV2 was overexpressed in CRC tissues, and it was closely correlated with depth of invasion, and lymph and distant metastasis. Multivariate analysis indicated that high NAV2 expression was a poor prognostic indicator of recurrence-free survival and overall survival in CRC patients. Furthermore, Cox regression analysis revealed that high NAV2 expression integrated with high tumor budding grade was a powerful independent predictive factor of CRC clinical outcome. In vitro and in vivo assays demonstrated that knockdown of NAV2 led to reduced migration and invasion of cancer cells, and the process involved the regulation of F-actin polymerization through the SSH1L/cofilin-1 pathway.ConclusionBased on these findings, NAV2 could serve as both a prognostic biomarker and a potential therapeutic target for patients with NAV2-positive CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0237-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Neuron navigator 2 overexpression indicates poor prognosis of colorectal cancer and promotes invasion through the SSH1L/cofilin-1 pathway

Tan¹,

Zhu²,

Tao³

et al. 2015

J Exp Clin Cancer Res

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“…According to the International Agency for Research on Cancer (IARC), in 2012, there were estimated to be 1.36 million new cases and 0.69 million deaths from CRC worldwide [ 3 ]. Currently, CRC treatment options include surgery, chemotherapy, radiotherapy, or a combination of the three [ 4 , 5 ]. Surgery is usually the first option, with the excision rate reaching 60–70% [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Use of Jianpi Jiedu Herbs in Patients with Advanced Colorectal Cancer: A Systematic Review and Meta‐Analysis

Zhang

Shi

Mao

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Objective To systematically review the effect of invigorating Pi and detoxification (Jianpi Jiedu, (JPJD)) herbs in advanced colorectal cancer (CRC) patients receiving chemotherapy. Methods Three English and four Chinese databases were searched. Literature was screened by EndNote X7 and data were analyzed by RevMan 5.2. Results This review comprised 12 randomized clinical studies of 701 patients. The results showed that JPJD herbs improved the therapeutic effect on Chinese medicine symptoms [risk ratio (RR) = 1.59; 95% confidence interval (CI): 1.35~1.88] and Karnofsky performance score [RR = 2.07; 95% CI: 1.52~2.82] for advanced CRC patients receiving chemotherapy, lowered the Chinese medicine symptoms' score [weighted mean difference = −2.44; 95% CI: −3.23~−1.64], reduced the incidence of nausea and vomiting [RR = 0.23; 95% CI: 0.11~0.49], improved platelet at toxicity grades III-IV [odds ratio = 0.29; 95% CI: 0.12~0.74] and I–IV [RR = 0.65; 95% CI: 0.51~0.82], and improved white blood cell at toxicity grades III-IV [RR = 0.37; 95% CI: 0.23~0.58] and I–IV [RR = 0.69; 95% CI: 0.60~0.79]. However, the results showed no significant effect on tumor response. Conclusion JPJD herbs can improve quality of life, relieve symptoms, and reduce adverse events of advanced CRC patients receiving chemotherapy.

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“…Survival analysis revealed that a low HLTF expression was associated with a poor prognosis. Metastasis is characterized by a series of pathological events, including deep invasion into the intestinal wall and the lymphovascular or circulatory systems (37). We then examined the motility of CRC cells when HLTF was knocked down or overexpressed.…”

Section: Discussionmentioning

confidence: 99%

HLTF suppresses the migration and invasion of colorectal cancer cells via TGF‑β/SMAD signaling in vitro

Liu

Zhou

et al. 2018

Int J Oncol

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Helicase-like transcription factor (HLTF) has been identified as a tumor suppressor gene. The hypermethylation of HTLF is frequently observed in various types of cancer, including colorectal cancer (CRC). However, the mechanisms through which HLTF suppresses CRC progression remain unclear. Thus, the aim of the present study was to explore the biological function of HLTF in CRC cells and the underlying mechanisms. CRC tissues and cells were used to detect the expression of HLTF. Wound-healing and Transwell assays were performed to assess the motility of CRC cells. The results revealed that HLTF expression was significantly associated with the differentiation status, invasion depth, lymph node metastasis and distant metastasis. A low HLTF expression was significantly associated with a poor survival. Furthermore, HTLF knockdown or ectopic overexpression significantly promoted or suppressed the motility of CRC cells, respectively. With regard to the underlying molecular mechanisms, the protein expression of HTLF was upregulated when the CRC cells were stimulated with transforming growth factor (TGF)-β, and HLTF upregulation induced an increase in SMAD4 and p-SMAD2/3 expression and a decrease in levels of the TGF-β/SMAD pathway downstream genes, Vimentin and zinc finger e-box binding homeobox 1 (ZEB1). On the whole, the findings of this study suggest that HLTF is negatively associated with the progression of CRC, and its overexpression suppresses the migration and invasion of CRC cells by targeting the TGF-β/SMAD pathway.

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Understanding the routes of metastasis in colorectal cancer

Cited by 18 publications

References 1 publication

Neuron navigator 2 overexpression indicates poor prognosis of colorectal cancer and promotes invasion through the SSH1L/cofilin-1 pathway

Neuron navigator 2 overexpression indicates poor prognosis of colorectal cancer and promotes invasion through the SSH1L/cofilin-1 pathway

Use of Jianpi Jiedu Herbs in Patients with Advanced Colorectal Cancer: A Systematic Review and Meta‐Analysis

HLTF suppresses the migration and invasion of colorectal cancer cells via TGF‑β/SMAD signaling in vitro

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