AKT Regulation of Growth and Proliferation

Inhibition of Pol I transcription treats murine and human AML by targeting the leukemia-initiating cell population

N Hein, DP Cameron, KM Hannan, NYN Nguyen, CY Fong, J Sornkom, M Wall, M Pavy, C Cullinane, J Diesch, JR Devlin, AJ George, E Sanij, J Quin, G Poortinga, I Verbrugge, A Baker, D Drygin, SJ Harrison, JD Rozario

2017-05-25

Despite the development of novel drugs, the prospects for many patients with acute myeloid leukemia (AML) remain dismal. This stud..

Cell cycle and growth stimuli regulate different steps of RNA polymerase I transcription

SS Hung, A Lesmana, A Peck, R Lee, E Tchoubrieva, KM Hannan, J Lin, KE Sheppard, K Jastrzebski, LM Quinn, LI Rothblum, RB Pearson, RD Hannan, E Sanij

2017-05-15

Transcription of the ribosomal RNA genes (rDNA) by RNA polymerase I (Pol I) is a major control step for ribosome synthesis and is ..

The potential of targeting ribosome biogenesis in high-grade serous ovarian cancer

S Yan, D Frank, J Son, KM Hannan, RD Hannan, KT Chan, RB Pearson, E Sanij

2017-01-20

Overall survival for patients with ovarian cancer (OC) has shown little improvement for decades meaning new therapeutic options ar..

Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription

J Kang, EP Kusnadi, AJ Ogden, RJ Hicks, L Bammert, U Kutay, S Hung, E Sanij, RD Hannan, KM Hannan, RB Pearson

2016-01-01

Dysregulation of RNA polymerase I (Pol I)-dependent ribosomal DNA (rDNA) transcription is a consistent feature of malignant transf..

Combination therapy targeting ribosome biogenesis and mRNA translation synergistically extends survival in MYC-driven lymphoma

JR Devlin, KM Hannan, N Hein, C Cullinane, E Kusnadi, PY Ng, AJ George, J Shortt, MJ Bywater, G Poortinga, E Sanij, J Kang, D Drygin, S O’Brien, RW Johnstone, GA McArthur, RD Hannan, RB Pearson

2016-01-01

Ribosome biogenesis and protein synthesis are dysregulated in many cancers, with those driven by the proto-oncogene c-MYC characte..

Inhibition of RNA polymerase I transcription initiation by CX-5461 activates non-canonical ATM/ATR signaling

J Quin, KT Chan, JR Devlin, DP Cameron, J Diesch, C Cullinane, J Ahern, A Khot, N Hein, AJ George, KM Hannan, G Poortinga, KE Sheppard, KK Khanna, RW Johnstone, D Drygin, GA McArthur, RB Pearson, E Sanij, RD Hannan

2016-01-01

RNA polymerase I (Pol I)-mediated transcription of the ribosomal RNA genes (rDNA) is confined to the nucleolus and is a rate-limit..

Regulation of rDNA transcription in response to growth factors, nutrients and energy

EP Kusnadi, KM Hannan, RJ Hicks, RD Hannan, RB Pearson, J Kang

2015-01-01

Exquisite control of ribosome biogenesis is fundamental for the maintenance of cellular growth and proliferation. Importantly, syn..

Targeting the nucleolus for cancer intervention

JE Quin, JR Devlin, D Cameron, KM Hannan, RB Pearson, RD Hannan

2014-01-01

The contribution of the nucleolus to cancer is well established with respect to its traditional role in facilitating ribosome biog..

Synergistic inhibition of ovarian cancer cell growth by combining selective PI3K/mTOR and RAS/ERK pathway inhibitors

KE Sheppard, C Cullinane, KM Hannan, M Wall, J Chan, F Barber, J Foo, D Cameron, A Neilsen, P Ng, J Ellul, M Kleinschmidt, KM Kinross, DD Bowtell, JG Christensen, RJ Hicks, RW Johnstone, GA McArthur, RD Hannan, WA Phillips

2013-12-01

Background Ovarian cancer is the major cause of death from gynaecological malignancy with a 5 year survival of only ∼30% due to re..

AKT signalling is required for ribosomal RNA synthesis and progression of Eμ-Myc B-cell lymphoma in vivo

JR Devlin, KM Hannan, PY Ng, MJ Bywater, J Shortt, C Cullinane, GA McArthur, RW Johnstone, RD Hannan, RB Pearson

2013-11-01

The dysregulation of PI3K/AKT/mTORC1 signalling and/or hyperactivation of MYC are observed in a high proportion of human cancers, ..

The mTORC1 inhibitor everolimus prevents and treats Eμ-Myc lymphoma by restoring oncogene-induced senescence

M Wall, G Poortinga, KL Stanley, RK Lindemann, M Bots, CJ Chan, MJ Bywater, KM Kinross, MV Astle, K Waldeck, KM Hannan, J Shortt, MJ Smyth, SW Lowe, RD Hannan, RB Pearson, RW Johnstone, GA McArthur

2013-01-01

MYC deregulation is common in human cancer. IG-MYC translocations that are modeled in EμMyc mice occur in almost all cases of Burk..

AKT induces senescence in human cells via mTORC1 and p53 in the absence of DNA damage: Implications for targeting mTOR during malignancy

MV Astle, KM Hannan, PY Ng, RS Lee, AJ George, AK Hsu, Y Haupt, RD Hannan, RB Pearson

2012-04-12

The phosphatidylinositol 3-kinase (PI3K)/AKT and RAS oncogenic signalling modules are frequently mutated in sporadic human cancer...

Drosophila ribosomal protein mutants control tissue growth non-autonomously via effects on the prothoracic gland and ecdysone

JI Lin, NC Mitchell, M Kalcina, E Tchoubrieva, MJ Stewart, SJ Marygold, CD Walker, G Thomas, SJ Leevers, RB Pearson, LM Quinn, RD Hannan

2011-12-01

The ribosome is critical for all aspects of cell growth due to its essential role in protein synthesis. Paradoxically, many Riboso..

Relative expression levels rather than specific activity plays the major role in determining in vivo AKT isoform substrate specificity

RS Lee, CM House, BE Cristiano, RD Hannan, RB Pearson, KM Hannan

2011-12-01

The AKT protooncogene mediates many cellular processes involved in normal development and disease states such as cancer. The three..

AKT promotes rRNA synthesis and cooperates with c-MYC to stimulate ribosome biogenesis in cancer

JC Chan, KM Hannan, K Riddell, PY Ng, A Peck, RS Lee, S Hung, MV Astle, M Bywater, M Wall, G Poortinga, K Jastrzebski, KE Sheppard, BA Hemmings, MN Hall, RW Johnstone, GA McArthur, RD Hannan, RB Pearson

2011-08-30

Precise regulation of ribosome biogenesis is fundamental to maintain normal cell growth and proliferation, and accelerated ribosom..

A phospho-proteomic screen identifies novel S6K1 and mTORC1 substrates revealing additional complexity in the signaling network regulating cell growth

K Jastrzebski, KM Hannan, CM House, SSC Hung, RB Pearson, RD Hannan

2011-08-01

S6K1, a critical downstream substrate of mTORC1, has been implicated in regulating protein synthesis and a variety of processes th..

Signaling to the ribosome in cancer - It is more than just mTORC1

KM Hannan, E Sanij, N Hein, RD Hannan, RB Pearson

2011-02-01

It is becoming increasingly clear that dysregulation of protein synthesis contributes to a range of diseases characterized by tiss..