Osteopontin production by TM4SF4 signaling drives a positive feedback autocrine loop with the STAT3 pathway to maintain cancer stem cell-like properties in lung cancer cells

Choi, Soo Im; Kim, Seo Yoen; Lee, Jei Ha; Kim, Jung Yul; Cho, Eun Wie; Kim, In-Gyu

doi:10.18632/oncotarget.21021

Cited by 32 publications

(31 citation statements)

References 54 publications

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“…Given that the mouse primary hepatocytes are different from rat hepatocyte cell line, we hypothesized that this difference might be due to differences in the cell types used as materials for studying. Furthermore, the expression of p-STAT3 was significantly attenuated after rrOPN treatment, which is not contrary to the results of some previous studies, where OPN could activate STAT3 signaling pathway and drive a positive feedback with STAT3 signaling pathway in some cancer cells [14,30]. Of note, the expression of p-STAT3 did not change obviously after treatment with OPN-siRNA or OPN-Ab, which is different from that in BRL-3A cells over-expressing OPN or rrOPN-treated BRL-3A cells.…”

Section: Discussioncontrasting

confidence: 92%

“…In view of the important roles of OPN during LR and the results of our previous studies, we hypothesized that OPN can directly promote rat hepatocyte proliferation. On the other hand, it is generally acknowledged that OPN could perform its functions though PI3K/Akt, MAPK, NF-jB and JAK/STAT signaling pathways by binding to a number of integrin receptors or CD44 in various cancer cells [12][13][14]. Wen et al have confirmed the role of OPN-mediated IL-6/Stat3 signaling pathway during the early phase of mouse LR [5].…”

Section: Introductionmentioning

confidence: 99%

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Osteopontin promotes rat hepatocyte proliferation both in vitro and in vivo

Wang

Chu

Chen

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Aim: This study aimed to examine the effects of osteopontin (OPN) on hepatocyte growth and liver regeneration (LR). Methods: A recombinant lentivirus expressing OPN and OPN-siRNAs were used to treat BRL-3A cells, while the adenovirus expressing OPN or OPN-targeted shRNA were applied for rat primary hepatocytes. Moreover, rrOPN and OPN-Ab were added to treat BRL-3A. Next, rrOPN was administrated into rat regenerating livers. Then in vitro and in vivo assays were performed to evaluate the biological function of OPN in hepatocyte growth and LR. Results: OPN overexpression facilitated proliferation and viability of BRL-3A cells and primary hepatocytes, while OPN silencing reversed these effects. Similarly, rrOPN stimulated cell cycle progression and viability, but OPN-Ab led to cell cycle arrest and decreased viability. OPN overexpression induced the expression of p-STAT3, p-AKT and CCND1, and OPN siRNA led to reduction of p-AKT and CCND1. Furthermore, rrOPN promoted the expression of p-STAT3 and p-AKT, while OPN-Ab and PI3K/Akt inhibitor LY294002 both inhibited the expressions of p-AKT and Bcl2. Moreover, LR rate, serum IL-6 and TNFa, Ki-67 þ proportion and the phosphorylation of STAT3, AKT and p65 were augmented by rrOPN treatment. Conclusion: OPN promotes hepatocyte proliferation both in vitro and in vivo through STAT3 and AKT signaling pathways.

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Section: Discussioncontrasting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Osteopontin promotes rat hepatocyte proliferation both in vitro and in vivo

Wang

Chu

Chen

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Reciprocally, AP-1 regulates the expression of osteopontin directly through binding to its promoter to mediate the tumorigenic properties of cancer cells [ 66 ]. Osteopontin is involved in autocrine loops that mediate RAS induced transformation of NIH3T3 cells [ 67 ] and EMT and stem cell like properties in lung cancer [ 68 ]. Another factor that plays an important paracrine role to regulate the angiogenic activity of the cancer cells is VEGF.…”

Section: Discussionmentioning

confidence: 99%

The role of AP-1 in self-sufficient proliferation and migration of cancer cells and its potential impact on an autocrine/paracrine loop

et al. 2018

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Activating protein-1 (AP-1) family members, especially Fra-1 and c-Jun, are highly expressed in invasive cancers and can mediate enhanced migration and proliferation. The aim of this study was to explore the significance of elevated levels of AP-1 family members under conditions that restrict growth. We observed that invasive MDA-MB-231 cells express high levels of Fra-1, c-Jun, and Jun-D during serum starvation and throughout the cell cycle compared to non-tumorigenic and non-invasive cell lines. We then analyzed Fra-1 levels in additional breast and other cancer cell lines. We found breast and lung cancer cells with higher levels of Fra-1 during serum starvation had relatively higher ability to proliferate and migrate under these conditions. Utilizing a dominant negative construct of AP-1, we demonstrated that proliferation and migration of MDA-MB-231 in the absence of serum requires AP-1 activity. Finally, we observed that MDA-MB-231 cells secrete factors(s) that induce Fra-1 expression and migration in non-tumorigenic and non-metastatic cells and that both the expression of and response to these factors require AP-1 activity. These results suggest the presence of an autocrine/paracrine loop that maintains high Fra-1 levels in aggressive cancer cells, enhancing their proliferative and metastatic ability and affecting neighbors to alter the tumor environment.

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“…Osteopontin (OPN)/integrin complex upregulates the expression of CD44 variants. OPN binding to CD44 enhances metastasis and generation of CSC through activation of STAT3 [181][182][183]. Additionally, OPN as a tumor biomarker is induced through the TM4SF4/GSK3β/β-catenin axis, JAK2/STAT3, and FAK/STAT3 signaling, and is additionally regulated via formation of positive feedback autocrine loop that results in cells acquiring CSC-like properties [183].…”

Section: Link Between Jak2/stat3 Activation and The Transition Of Canmentioning

confidence: 99%

Role of JAK/STAT3 Signaling in the Regulation of Metastasis, the Transition of Cancer Stem Cells, and Chemoresistance of Cancer by Epithelial–Mesenchymal Transition

Jin

2020

Cells

294

193

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The JAK/STAT3 signaling pathway plays an essential role in various types of cancers. Activation of this pathway leads to increased tumorigenic and metastatic ability, the transition of cancer stem cells (CSCs), and chemoresistance in cancer via enhancing the epithelial–mesenchymal transition (EMT). EMT acts as a critical regulator in the progression of cancer and is involved in regulating invasion, spread, and survival. Furthermore, accumulating evidence indicates the failure of conventional therapies due to the acquisition of CSC properties. In this review, we summarize the effects of JAK/STAT3 activation on EMT and the generation of CSCs. Moreover, we discuss cutting-edge data on the link between EMT and CSCs in the tumor microenvironment that involves a previously unknown function of miRNAs, and also discuss new regulators of the JAK/STAT3 signaling pathway.

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Osteopontin production by TM4SF4 signaling drives a positive feedback autocrine loop with the STAT3 pathway to maintain cancer stem cell-like properties in lung cancer cells

Abstract: ABSTRACT

Cited by 32 publications

References 54 publications

Osteopontin promotes rat hepatocyte proliferation both in vitro and in vivo

Osteopontin promotes rat hepatocyte proliferation both in vitro and in vivo

The role of AP-1 in self-sufficient proliferation and migration of cancer cells and its potential impact on an autocrine/paracrine loop

Role of JAK/STAT3 Signaling in the Regulation of Metastasis, the Transition of Cancer Stem Cells, and Chemoresistance of Cancer by Epithelial–Mesenchymal Transition

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