PODXL, negatively regulated by KLF4, promotes the EMT and metastasis and serves as a novel prognostic indicator of gastric cancer

Zhang, Jing; Zhu, Zhongqi; Wu, Hongyan; Yu, Zhuang; Rong, Zeyin; Luo, Zai; Xu, Yi‐Wei; Huang, Kai-Wen; Qiu, Zhengjun; Huang, Chen

doi:10.1007/s10120-018-0833-y

Cited by 47 publications

(43 citation statements)

References 33 publications

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“…Accordingly, forced expression of PODXL in A549 cells promoted changes characteristic of EMT through a process dependent on the activation of PI3K/AKT signaling pathway [87]. Similarly, PODXL silencing in HCT15 colon cancer cells and in SGC-7901 and AGS gastric cancer cells led to a reduction of EMT-associated markers [51,54]. Moreover, the analysis of mRNA expression levels in patients with colon cancer using GSE17536 datasets revealed a positive correlation of PODXL expression with the mesenchymal markers vimentin, N-cadherin, TWIST2, SLUG, and ZEB1 and a negative correlation with the epithelial marker E-cadherin [54].…”

Section: Podxl In Emtmentioning

confidence: 92%

“…On the other hand, PODXL overexpression in MCF-7 breast cancer cell line stimulated invadopodia formation and activation, through the induction of Rac1/Cdc42/cortactin signaling [82]. The migratory and invasive properties promoted by PODXL has also been demonstrated in vitro in colorectal cancer (HCT116, LOVO and HCT15), gastric cancer (SGC-7901, AGS, BGC823, and MGC803), malignant testicular tumor (NT2), oral squamous cell carcinoma (SAS), lung adenocarcinoma (A549), and glioblastoma multiforme (LN-299 and U-118) cell lines [32,46,51,54,[75][76][77][78]87]. Besides, silencing of PODXL in both NAMEC8R and the highly metastatic MDA-MB-231 4175 breast cancer cells decreased extravasation in vitro, an effect which was totally reversed by overexpressing wild type PODXL [81].…”

Section: Podxl In Metastasismentioning

confidence: 95%

“…In NAMEC8R, MDA-MB-231, and MDA-MB-231 clone 4175 breast cancer cells, knockdown of PODXL significantly inhibited tumor dissemination to distant organs in murine xenograft models [80][81][82], an effect rescued by re-expressing wild type PODXL [81]. In SGC-7901 and AGS gastric cancer cells, silencing of PODXL impaired liver metastasis in nude mice [51]. Recently, depletion of PODXL has been found to reduce liver metastasis in a hemispleen mouse model using SW1990 and Pa03c pancreatic adenocarcinoma cells [83].…”

Section: Podxl In Metastasismentioning

confidence: 96%

“…The PI3K/AKT pathway is one of the most commonly activated drivers of cancer and promotes tumor initiation and progression [91,92]. PODXL in SGC-7901 and AGS gastric cancer cells also enhanced primary tumor growth in nude mice [51]. In HCT15 colorectal cells, knockdown of PODXL reduced the expression of TAZ protein, its downstream targets survivin, connective tissue growth factor (CTGF), CYR61 and cyclinD1, and stem-cell-related genes, as well as tumorsphere formation, indicating that PODXL plays a crucial role in self-renewal of colon cancer cells [54].…”

Section: Burkitt Lymphoma Raji Ectopic Overexpression Of Podxlmentioning

confidence: 99%

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Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

Tamayo-Orbegozo

Amo

Díez-García

et al. 2020

Cancers

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Mature B-cell non-Hodgkin lymphoma (B-NHL) constitutes a group of heterogeneous malignant lymphoproliferative diseases ranging from indolent to highly aggressive forms. Although the survival after chemo-immunotherapy treatment of mature B-NHL has increased over the last years, many patients relapse or remain refractory due to drug resistance, presenting an unfavorable prognosis. Hence, there is an urgent need to identify new prognostic markers and therapeutic targets. Podocalyxin (PODXL), a sialomucin overexpressed in a variety of tumor cell types and associated with their aggressiveness, has been implicated in multiple aspects of cancer progression, although its participation in hematological malignancies remains unexplored. New evidence points to a role for PODXL in mature B-NHL cell proliferation, survival, migration, drug resistance, and metabolic reprogramming, as well as enhanced levels of PODXL in mature B-NHL. Here, we review the current knowledge on the contribution of PODXL to tumorigenesis, highlighting and discussing its role in mature B-NHL progression.

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Section: Podxl In Emtmentioning

confidence: 92%

Section: Podxl In Metastasismentioning

confidence: 95%

Section: Podxl In Metastasismentioning

confidence: 96%

Section: Burkitt Lymphoma Raji Ectopic Overexpression Of Podxlmentioning

confidence: 99%

See 2 more Smart Citations

Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

Tamayo-Orbegozo

Amo

Díez-García

et al. 2020

Cancers

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“…Krüppel‐like factor 4 played a negative role in gastric cancer cell invasion, which was reversed by upregulation of serine/threonine kinase 33 expression at the transcriptional level 20 . Our previous studies found that loss of KLF4 expression contributed to enhance human gastric cancer EMT and metastasis development and progression through regulating PODXL 21 . However, the underlying molecular mechanism of the tumor‐suppressive role of KLF4 in CRC is still vague, and needs to be further investigated.…”

Section: Introductionmentioning

confidence: 91%

GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel‐like factor 4, promotes the growth of colorectal cancer

et al. 2020

Self Cite

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| 1203 wileyonlinelibrary.com/journal/cas | INTRODUC TI ONColorectal cancer is the third most common tumor and the third leading cause of cancer-related death in man and women in the world. 1,2 In China, there was an increase of over 376 300 cases of CRC and a total of 191 000 deaths during 2015. 3 Environmental and lifestyle changes, including an altered diet, lack of appropriate physical activity, circadian disruption, and increase in alcohol consumption, have enormously aggravated the burden of CRC. 4 In the past several years, the incidence and mortality of CRC increased rapidly and the onset age was muchThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractGINS complex subunit 4 (GINS4) is essential for DNA replication initiation and elongation in the G 1 /S phase cell cycle in eukaryotes, however, its functional roles and molecular mechanisms remain unclear in many aspects. Our study was designed to investigate the clinical significance, biological function, and molecular mechanism of GINS4 in colorectal cancer (CRC). First, we confirmed that GINS4 expression was significantly overexpressed in CRC cells and tissues. The immunohistochemical results in tissue microarray from 106 CRC patients showed that a high level of GINS4 expression was positively correlated with advanced T stage, higher tumor TNM stage, and poor differentiation. The results from univariate and multivariate survival analysis models based on 106 CRC patients revealed that GINS4 might serve as an independent prognostic indicator for overall survival and disease-free survival of CRC patients.Moreover, downregulated GINS4 can inhibit growth and the cell cycle and accelerate cell apoptosis progression in vitro as well as inhibit tumorigenesis in vivo. Besides, our results also indicated that Krüppel-like factor 4 (KLF4) can negatively regulate GINS4 expression at the transcriptional level and the KLF/GINS4 pathway might play a vital role in the growth and prognosis of CRC. K E Y W O R D Sbiomarker, colorectal cancer, GINS4, growth, KLF4

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Helicobacter pylori CagA promotes the malignant transformation of gastric mucosal epithelial cells through the dysregulation of the miR‐155/KLF4 signaling pathway

Ren

Zhao

et al. 2019

Molecular Carcinogenesis

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The Helicobacter pylori (H. pylori) cytotoxin-associated gene A (CagA) and Krüppel-like transcription factor (KLF4) were both closely associated with the development and progression of gastric cancer (GC). However, the nature of the interactions between CagA and KLF4 in GC development has not been elucidated. Therefore, we focused on the CagA-mediated promotion of the malignant transformation of gastric epithelial cells. Herein, we first examined the expression of KLF4 in both human cancer and paracarcinoma tissues with or without H. pylori infection and found that KLF4 expression was significantly decreased in H. pylori-positive GC cells compared with the H. pylori-negative GC cells. Further functional studies revealed that the increased expression of CagA could suppress KLF4 expression and promote the malignant transformation of normal epithelial cells. Subsequently, we found that CagA could upregulate miR-155 and further restrict the expression of downstream KLF4. More importantly, the overexpression of miR-155 in GES-1 promoted epithelial-mesenchymal transition and eventually facilitated tumor growth in vivo. Overall, the identification of the CagA/miR-155/KLF4 signaling pathway provided a new insight into the development and treatment of GC. K E Y W O R D S CagA, gastric cancer, Helicobacter pylori, Krüppel-like factor 4, miR-155

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PODXL, negatively regulated by KLF4, promotes the EMT and metastasis and serves as a novel prognostic indicator of gastric cancer

Abstract: KLF4/PODXL signaling pathway assumes an irreplaceable role in tumorigenesis, invasion and metastasis of human GC and PODXL serves as an independent prognostic indicator for GC patients.

Cited by 47 publications

References 33 publications

Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel‐like factor 4, promotes the growth of colorectal cancer

Helicobacter pylori CagA promotes the malignant transformation of gastric mucosal epithelial cells through the dysregulation of the miR‐155/KLF4 signaling pathway

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