Inactivation of AMPK alters gene expression and promotes growth of prostate cancer cells

Zhou, Jing; Huang, Wei; Tao, Ran; Ibaragi, Soichiro; Lan, Fang; Ido, Yasuo; Wu, Xin; Alekseyev, Yuriy O.; Lenburg, Marc E.; Hu, G-f.; Luo, Zhijun

doi:10.1038/onc.2009.63

Cited by 106 publications

(98 citation statements)

References 40 publications

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“…31 Indeed, the LKB1/AMPK pathway is clearly involved in the regulation of cell growth of gastrointestinal hamartomas and many other malignancies including those arising in colon, breast, ovarian, pancreatic and lung tissues (the so called Peutz-Jeghers Syndrome, PJS), as well as in melanoma, breast and prostate cancer. [31][32][33][34][35] AMPK is able to associate with and phosphorylate FoxO both in nematodes and mammalian cells. In nematodes, AMPK phosphorylates FoxO on six residues: T166, S202, S314, S321, T463 and S466.…”

Section: The Ampk-foxo Axis: Balancing Nutrient Sensing and Healthspamentioning

confidence: 99%

The AMPK-FoxO3A axis as a target for cancer treatment

Chiacchiera¹,

Simone²

2010

Cell Cycle

156

142

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Section: The Ampk-foxo Axis: Balancing Nutrient Sensing and Healthspamentioning

confidence: 99%

The AMPK-FoxO3A axis as a target for cancer treatment

Chiacchiera¹,

Simone²

2010

Cell Cycle

156

142

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“…Either AKT inhibition or AMPK activation suppresses prostate cancer growth (23). Therefore, we investigated whether the combined modulation of AKT and AMPK is more effective than either alone in prostate cancer therapy.…”

Section: Geraniol Inhibits Akt-mtor Signaling In Pc-3 Cellsmentioning

confidence: 99%

“…AMPK also interferes with AKT signaling by phosphoryGeraniol induces cooperative interaction of apoptosis and autophagy to elicit cell death in PC-3 prostate cancer cells lating TSC2 and/or Raptor, which inhibits mTOR activity (22). AMPK inhibition accelerated cell proliferation and promoted malignant behavior (23). These findings suggest that the anticancer effects of AKT inhibition may be potentiated by AMPK activation.…”

Section: Introductionmentioning

confidence: 99%

Geraniol induces cooperative interaction of apoptosis and autophagy to elicit cell death in PC-3 prostate cancer cells

Jeon

2011

Int J Oncol

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Abstract. Geraniol, an acyclic dietary monoterpene, suppresses prostate cancer growth and enhances docetaxel chemosensitivity in cultured cell or xenograft tumor models. However, the mechanisms of the geraniol action against prostate cancer are largely unknown. In this study, we investigated the cellular and molecular mechanisms of geraniol-induced cell death in PC-3 prostate cancer cells. Among the examined structurally and functionally similar monoterpenes, geraniol potently induced apoptosis and autophagy. Although independent processes, apoptosis and autophagy acted as cooperative partners to elicit geraniol-induced cell death in PC-3 cells. At a molecular level, geraniol inhibited AKT signaling and activated AMPK signaling, resulting in mTOR inhibition. Combined treatment of AKT inhibitor and AMPK activator markedly suppressed cell growth compared to either treatment alone. Our findings provide insight into future investigations that are aimed at elucidating the role of apoptosis and autophagy in prostate cancer therapy and at developing anticancer strategies co-targeting AKT and AMPK.

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“…[1][2][3][4] In this regard, we are beginning to accumulate substantial evidence indicating that the metabolic fuel gauge AMPK can also function as a canonical suppressor of cell proliferation: [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] (1) AMPK activation promotes the maintenance of a resting cell phenotype in mature tissues which do not require proliferation to keep its function; (2) an enhanced activity of AMPK further renders normal cells resistant to oncogenic transformation, and (3) Pharmacological hyperactivation of AMPK in cancer cells results in reduced cell growth both in vitro and in vivo. Not surprisingly, AMPK sits in-between bona fide tumor-suppressors in the complex signaling process that controls cell proliferation, namely the upstream activating AMPK Kinase LKB1 and the downstream AMPK effectors p53 and Tuberous sclerosis-2 (TSC2).…”

Section: Introductionmentioning

confidence: 99%

The active form of the metabolic sensor AMP-activated protein kinase α (AMPKα) directly binds the mitotic apparatus and travels from centrosomes to the spindle midzone during mitosis and cytokinesis

Vázquez-Martín

Oliveras‐Ferraros²,

Menéndez³

2009

Cell Cycle

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(2009) The active form of the metabolic sensor AMP-activated protein kinase α (AMPKα) directly binds the mitotic apparatus and travels from centrosomes to the spindle midzone during mitosis and cytokinesis, Cell Cycle, 8:15, 2385Cycle, 8:15, -2398 The metabolic rheostat AMP-activated protein kinase (AMPK) is unexpectedly required for proper cell division and faithful chromosomal segregation during mitosis. Although it is conceptually attractive to assume that AMPK-interpreted microenvironmental bioenergetics may strictly engage cell's energy status, cell grow, and cell division to avoid that energy stresses trigger cell death, the ultimate framework of AMPK activity towards chromosomal and cytoskeletal mitotic regulation is a question that remains unanswered. We herein reveal that the active form of the α-catalytic AMPK subunit (P-AMPKα Thr172 )-but not its total form (AMPKα)-transiently associates with several mitotic structures including centrosomes, spindle poles, the central spindle midzone and the midbody throughout all of the mitotic stages and cytokinesis in human cancer-derived epithelial cells. At prophase, P-AMPKα Thr172 associates with the two asters of microtubules that begin to nucleate from mature centrosomes. The overlapping localization of P-AMPKα Thr172 with the mitotic centrosomal Aurora-A kinase is also apparent on the microtubules near the spindle poles in metaphase and in early anaphase. This Aurora A-like centrosomal localization of P-AMPKα Thr172 cannot be detected following chromatid separation following anaphase-telophase transition. Rather, toward the end of anaphase and in telophase P-AMPKα Thr172 reactivity exhibited a similar but not identical localization to that occupied by the bona fide chromosomal passenger proteins INCENCP and Aurora-B. This localization of P-AMPKα Thr172 at the central spindle and midbody persisted during the furrowing process and, at the completion of telophase, staining of P-AMPKα Thr172 as doublet was apparent on either side of the midbody within the intercellular cytokinetic bridge. An identical mitotic geography of P-AMPKα Thr172 was observed in cancer cells lacking the AMPK kinase LKB1, in non-cancerous human epithelial cells, and in mouse fibroblasts. The active form of AMPKα bound to the mitotic apparatus may physically tether the bioenergetic state of a cell to the four-dimensional regulation of the chromosomal and cytoskeletal mitotic events, thus suggesting a putative cytokinetic suppressor function. In this newly discovered scenario, we suggest a primordial mitotic role for the α catalytic AMPK subunit in the eukaryotic evolutionary process as it may ensure, at the cell level, an exquisite coordination between sensing of energy resources and the fundamental biological process of genome division.

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Inactivation of AMPK alters gene expression and promotes growth of prostate cancer cells

Cited by 106 publications

References 40 publications

The AMPK-FoxO3A axis as a target for cancer treatment

The AMPK-FoxO3A axis as a target for cancer treatment

Geraniol induces cooperative interaction of apoptosis and autophagy to elicit cell death in PC-3 prostate cancer cells

The active form of the metabolic sensor AMP-activated protein kinase α (AMPKα) directly binds the mitotic apparatus and travels from centrosomes to the spindle midzone during mitosis and cytokinesis

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