STK25-induced inhibition of aerobic glycolysis via GOLPH3-mTOR pathway suppresses cell proliferation in colorectal cancer

Wu, Fan; Gao, Pin; Wu, Wei; Wang, Zaozao; Yang, Jie; Di, Jiabo; Jiang, Beihai; Su, Xiangqian

doi:10.1186/s13046-018-0808-1

Cited by 34 publications

(47 citation statements)

References 40 publications

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“…Very strikingly, altered expression of GOLPH3 and Myosin-18A are associated with a range of malignant phenotypes including tumour secretion (41), increased trafficking to the leading edge of migratory cells and consequently augmented cell motility, loss of cell-cell adhesion and invasion (39,45,49,50,(218)(219)(220)(221)(222)(223)(224)(225). However, while this model is strongly supported by a wealth of experimental data, there is at least one report indicating that Myosin-18A is neither localised to the Golgi nor required for its characteristic ribbon like structure (226).…”

Section: Golph3 -A Golgi Pi4p Effector and Oncoproteinmentioning

confidence: 99%

“…Hence there is a clear mechanistic pathway linking a known carcinogenic event with abnormal PI4Pdependent membrane trafficking (55). In addition, other studies have indicated that the range of non-trafficking GOLPH3 functions in cancer can be attributed to signalling activation, particularly of the AKT-mTOR signalling axis (34,39,44,49,(220)(221)(222)(223)(224)(225)(228)(229)(230)(231)(232)(233)(234)(235), and also that extra-Golgi pools of this protein that vary in size and impact depending on cell type (236). Hence, similar to the story with the Golgi PI 4-kinases, the entire repertoire of GOLPH3 dysfunctionality in cancer is unlikely to be restricted to augmented flux through the secretory pathway.…”

Section: Golph3 -A Golgi Pi4p Effector and Oncoproteinmentioning

confidence: 99%

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The Great Escape: how phosphatidylinositol 4-kinases and PI4P promote vesicle exit from the Golgi (and drive cancer)

Waugh

2019

Biochemical Journal

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Phosphatidylinositol 4-phosphate (PI4P) is a membrane glycerophospholipid and a major regulator of the characteristic appearance of the Golgi complex as well as its vesicular trafficking, signalling and metabolic functions. Phosphatidylinositol 4-kinases, and in particular the PI4KIIIβ isoform, act in concert with PI4P to recruit macromolecular complexes to initiate the biogenesis of trafficking vesicles for several Golgi exit routes. Dysregulation of Golgi PI4P metabolism and the PI4P protein interactome features in many cancers and is often associated with tumour progression and a poor prognosis. Increased expression of PI4P-binding proteins, such as GOLPH3 or PITPNC1, induces a malignant secretory phenotype and the release of proteins that can remodel the extracellular matrix, promote angiogenesis and enhance cell motility. Aberrant Golgi PI4P metabolism can also result in the impaired post-translational modification of proteins required for focal adhesion formation and cell–matrix interactions, thereby potentiating the development of aggressive metastatic and invasive tumours. Altered expression of the Golgi-targeted PI 4-kinases, PI4KIIIβ, PI4KIIα and PI4KIIβ, or the PI4P phosphate Sac1, can also modulate oncogenic signalling through effects on TGN-endosomal trafficking. A Golgi trafficking role for a PIP 5-kinase has been recently described, which indicates that PI4P is not the only functionally important phosphoinositide at this subcellular location. This review charts new developments in our understanding of phosphatidylinositol 4-kinase function at the Golgi and how PI4P-dependent trafficking can be deregulated in malignant disease.

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Section: Golph3 -A Golgi Pi4p Effector and Oncoproteinmentioning

confidence: 99%

Section: Golph3 -A Golgi Pi4p Effector and Oncoproteinmentioning

confidence: 99%

The Great Escape: how phosphatidylinositol 4-kinases and PI4P promote vesicle exit from the Golgi (and drive cancer)

Waugh

2019

Biochemical Journal

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“…STK25 suppressed aerobic glycolysis to repress cell proliferation in CRC by regulating GOLPH3-mTOR pathway [30]. Pim1 promoted CRC cell growth and tolerance to glucose starvation through enhancing the aerobic glycolysis [31].…”

Section: Discussionmentioning

confidence: 99%

“…For example, FOXC1 contributed to cell proliferation in CRC by enhancing the aerobic glycolysis through binding to FBP1 [29]. STK25 suppressed aerobic glycolysis to repress cell proliferation in CRC by regulating GOLPH3-mTOR pathway [30]. Pim1 promoted CRC cell growth and tolerance to glucose starvation through enhancing the aerobic glycolysis [31].…”

Section: Discussionmentioning

confidence: 99%

Circ-BANP Contributes to Cell Carcinogenesis and Aerobic Glycolysis by Regulating MAPK1 Through miR-874-3p in Colorectal Cancer

Zhang

Shen

Zha

et al. 2021

Preprint

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BackgroundCircular RNA-BTG3 associated nuclear protein (circ-BANP) was identifified to involve in cell proliferation of colorectal cancer (CRC). The aerobic glycolysis is a key metabolism mediating cancer progression. However, the role of circ-BANP on aerobic glycolysis in CRC remains unknown. MethodsThe expression of circ-BANP, microRNA (miR)-874-3p, and mitogen-activated protein kinase 1 (MAPK1) mNRA was detected using quantitative real-time polymerase chain reaction. Cell viability and invasion were measured by cell counting kit-8 assay or transwell assay. Glucose consumption and lactate production were assessed by a glucose and lactate assay kit. XF Extracellular Flux Analyzer was used to determine extracellular acidifification rate (ECAR). Western blot was used to analyze the levels of hexokinase-2 (HK2), pyruvate kinase M2 (PKM2), MAPK1, proliferating cell nuclear antigen (PCNA), Cyclin D1, N-cadherin, E-cadherin, hypoxia inducible factor-1α (HIF-1α), glucose transport protein 1(GLUT1), and c-Myc. The interaction between miR-874-3p and circ-BANP or MAPK1 was confifirmed by dual luciferase reporter assay. In vivo experiments were conducted through the murine xenograft model. ResultsCirc-BANP was up-regulated in CRC tissues and cell lines. Circ-BANP knockdown suppressed CRC cell proliferation, invasion and aerobic glycolysis in vitro as well as inhibited tumor growth in vivo. Circ-BANP was a sponge of miR-874-3p and performed anti-tumor effffects by binding to miR-874-3p in CRC cells. Subsequently, we confifirmed MAPK1 was a target of miR-874-3p and circ-BANP indirectly regulated MAPK1 expression by sponging miR-874-3p. After that, we found MAPK1 overexpression partially reversed circ-BANP deletion-mediated inhibition on cell carcinogenesis and aerobic glycolysis in CRC. ConclusionCirc-BANP accelerated cell carcinogenesis and aerobic glycolysis by regulating MAPK1 through miR- 874-3p in CRC, suggesting a promising therapeutic strategy for CRC treatment.

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“…Taken together, we identified a potential regulatory mechanism of p16 INK4a /MMP-2 expression in cancer by loss of function of p21 WAF1/Cip1 through the interaction with hYSK1 in hypoxia (Figure 6). Conversely, Wu et al [25] have demonstrated that STK25 (a.k.a hYSK1) suppressed the proliferation of human colorectal cancer cells and silencing STK25 enhanced xenograft tumor growth in mice. Thus, additional studies are warranted to define the exact role of hYSK1 in cancer.…”

Section: Discussionmentioning

confidence: 99%

p21WAF1/Cip1 Regulation by hYSK1 Activates SP-1 Transcription Factor and Increases MMP-2 Expression under Hypoxic Conditions

Lee

Kundu

Choi

2019

IJMS

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The hYSK1, a serine/threonine kinase (STK)-25, has been implicated in a variety of cellular functions including cell migration and polarity. We have recently reported that hYSK1 down-regulated the expression and functions of p16INK4a, a cell cycle regulatory protein, thereby enhancing migration and growth of cancer cells under hypoxic conditions. In this study, we further investigated the mechanisms underlying downregulation of p16INK4a and anti-migratory function of hYSK1. Our study revealed that p21WAF1/Cip1 is a novel binding partner of hYSK1. Moreover, the interaction between hYSK1 and p21WAF1/Cip1 led to the inhibition of SP-1 transcriptional activity, as revealed by a significant down-regulation of SP-1-mediated transactivation of p16INK4a promoter, and accelerated MMP-2 expression. Conversely, the knock-down of hYSK1 enhanced the p16INK4a promoter activity and protein expression, and diminished MMP-2 transcription and protein levels in hypoxic conditions as compared to control. Taken together, hYSK1 blocks the p21WAF1/Cip1 functions by direct interaction and inhibits the p16INK4a expression and induces MMP-2 expression by its regulations of SP-1 transcriptional activity under the hypoxia conditions.

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STK25-induced inhibition of aerobic glycolysis via GOLPH3-mTOR pathway suppresses cell proliferation in colorectal cancer

Cited by 34 publications

References 40 publications

The Great Escape: how phosphatidylinositol 4-kinases and PI4P promote vesicle exit from the Golgi (and drive cancer)

The Great Escape: how phosphatidylinositol 4-kinases and PI4P promote vesicle exit from the Golgi (and drive cancer)

Circ-BANP Contributes to Cell Carcinogenesis and Aerobic Glycolysis by Regulating MAPK1 Through miR-874-3p in Colorectal Cancer

p21WAF1/Cip1 Regulation by hYSK1 Activates SP-1 Transcription Factor and Increases MMP-2 Expression under Hypoxic Conditions

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