Knockdown of β-catenin controls both apoptotic and autophagic cell death through LKB1/AMPK signaling in head and neck squamous cell carcinoma cell lines

Chang, Hyo Won; Lee, Yoon Se; Nam, Hae Yun; Han, Myoung Wol; Kim, Hyo Jung; Moon, So Young; Jeon, Hyesung; Park, Jung Je; Carey, Thomas E.; Chang, Sung Eun; Kim, Seong Who; Kim, Sang Yoon

doi:10.1016/j.cellsig.2012.12.020

Cited by 54 publications

(54 citation statements)

References 35 publications

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“…In addition, the HeLa cell line is severely impaired in LKB1 activity (30). The present study showed that inducible expression of MARK2 in HeLa cells was sufficient to mimic LKB1 signaling activation as previously reported (12)(13)(14), and further confirms that MARK2 is a critical downstream target of LKB1.…”

Section: Discussionsupporting

confidence: 90%

“…When cellular AMP:ATP ratios rise, LKB1 directly phosphorylates the threonine 172 (Thr172) in the activation loop of AMPK and results in an increase in ATP-producing activities and a decrease in ATP-consuming processes including essentially all biosynthetic pathways required for cell growth (10,11). Previous investigations have shown that activation of the LKB1-AMPK pathway is able to suppress cell growth by arresting the cell cycle in the G1 phase (12,13). In a similar manner, we confirmed and extended these observations by demonstrating that exogenous activation of LKB1-AMPK signaling induces downregulation of cyclins (cyclin D1 and D3) and upregulation of the cyclin-dependent kinase (CDK) inhibitors (p53, p21 and p16), and thus, inhibits G1/S cell cycle transition, even in cells with endogenous expression of LKB1 (14).…”

Section: Introductionmentioning

confidence: 99%

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MARK2 inhibits the growth of HeLa cells through AMPK and reverses epithelial-mesenchymal transition

Xin

et al. 2017

Oncology Reports

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Abstract. Microtubule affinity-regulating kinases (MARKs; MARK1, MARK2, MARK3 and MARK4) act directly downstream of LKB1, the multitasking tumor-suppressor kinase, and thereby mediate its biological effects. Current understanding of the function of MARKs is greatly restricted to regulation of cell polarity. However, whether or how MARKs contribute to cellular growth control remains largely unknown. In the present study, we utilized an inducible lentiviral expression system that allows rapid MARK expression in LKB1-deficient HeLa cells, and characterized additional functions of MARKs: overexpression of MARK2 in HeLa cells resulted in a decrease in cell growth, inhibition of colony formation and arrest in G1 cell cycle phase, with AMPK as the putative downstream effector upregulating the expression of p21 and p16. MARK2 was found to play a role in F-actin reorganization and to contribute to reversal of epithelial-mesenchymal transition (EMT) as exemplified in the case of HeLa cells that exhibited phenotypic changes, reduced cell migration and invasion. Our findings unveil the coordinated regulation of cell growth and EMT mediated by MARK2, and also provide new insights into the mechanisms underlying the anti-metastatic activity of MARK2.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

MARK2 inhibits the growth of HeLa cells through AMPK and reverses epithelial-mesenchymal transition

Xin

et al. 2017

Oncology Reports

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“…Recent studies have shown that β-catenin signaling may play a role in autophagy in some models [10,11,12,13,14,15], whereas its involvement in autophagy in prostate cancer cells has not been addressed.…”

Section: Discussionmentioning

confidence: 99%

“…However, our knowledge on these contexts is rather limited. Recent studies have shown that Wnt/β-catenin signaling plays a role in autophagy in some models [10,11,12,13,14,15], but the involvement of this pathway in prostate cancer has not been reported. The Wnt signaling pathways are a group of signaling pathways that have been catalogued as the canonical Wnt pathway, the noncanonical planar cell polarity pathway and the noncanonical Wnt/calcium pathway.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Autophagy of Prostate Cancer Cells by β-Catenin Signaling

Lin

Feng

Shao-liang

et al. 2015

Cell Physiol Biochem

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Background/Aims: Autophagy is a cellular degradation process for the recycling of damaged or superfluous intracellular compartments to provide an alternative energy source during periods of metabolic stress for maintaining cell homeostasis and viability. Although autophagy in different contexts have been shown to use similar signaling pathways, the exact molecular regulation of autophagy has been found to be cell-type dependent. Methods: We used rapamycin to trigger autophagy and used nitric oxide (NO) to inhibit autophagy in prostate cancer cells. IWP-2 was used to inhibit β-catenin signaling. Autophagy-associated proteins were examined by Western blot. Results: We found that nitric oxide (NO), a potent cellular messenger, impaired rapamycin-induced autophagy in prostate cancer cells. Further analyses showed that NO induced nuclear accumulation of β-catenin, a key factor of Wnt signaling pathway, to inhibit autophagy in prostate cancer cells. Conclusions: We demonstrate involvement of β-catenin signaling in the regulation of autophagy of prostate cancer cells. Our results shed light on a previously unappreciated β-catenin signaling pathway for regulating autophagy in prostate cancer.

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“…The endostyle zone 4 tissues expressed the highest b-catenin levels (in both nuclei and cytoplasm) at blastogenic phases "A", "B" and early "C", and became dramatically down-expressed at advanced blastogenic phase "C", prior to the onset of the 'take over' process. Either knockdown (Chang et al, 2013) or overexpression (Kim et al, 2000) of b-catenin may induce apoptosis. In this study, though agonist treatment in blastogenic phase "A" treated colonies induced the premature destruction of internal organs in zooids, it did not accelerate the blastogenic cycle, but instead extended it.…”

Section: Discussionmentioning

confidence: 99%

The involvement of three signal transduction pathways in botryllid ascidian astogeny, as revealed by expression patterns of representative genes

Rosner¹,

Alfassi²,

Моисеева³

et al. 2014

Int. J. Dev. Biol.

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The patterning of the modular body plan in colonial organisms is termed astogeny, as distinct from ontogeny, the development of an individual organism from embryo to adult. Evolutionarily conserved signaling pathways suggest shared roots and common uses for both ontogeny and astogeny. Botryllid ascidians, a widely dispersed group of colonial tunicates, exhibit an intricate modular life form, in which astogeny develops as weekly, highly synchronized growth/ death cycles termed blastogenesis, abiding by a strictly regulated plan. In these organisms both astogeny and ontogeny form similar body structures.

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Knockdown of β-catenin controls both apoptotic and autophagic cell death through LKB1/AMPK signaling in head and neck squamous cell carcinoma cell lines

Cited by 54 publications

References 35 publications

MARK2 inhibits the growth of HeLa cells through AMPK and reverses epithelial-mesenchymal transition

MARK2 inhibits the growth of HeLa cells through AMPK and reverses epithelial-mesenchymal transition

Regulation of Autophagy of Prostate Cancer Cells by β-Catenin Signaling

The involvement of three signal transduction pathways in botryllid ascidian astogeny, as revealed by expression patterns of representative genes

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