Phosphoinositide signaling in cancer: INPP4B Akt(s) out

Woolley, J. C.; Dzneladze, Irakli; Salmena, Leonardo

doi:10.1016/j.molmed.2015.06.006

Cited by 24 publications

(26 citation statements)

References 10 publications

(26 reference statements)

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“…The review by Woolley et al23 summarized the mechanism underlying the complexity in function of INPP4B in cancer. Most of the previous studies identified INPP4B as a suppressor of oncogenic growth of cancer cells via the traditional PI3K/INPP4B/AKT axis, whereby INPP4B dephosphorylates PI(3,4)P2 to obstruct the activation of AKT.…”

Section: Discussionmentioning

confidence: 99%

INPP4B restrains cell proliferation and metastasis via regulation of the PI3K/AKT/SGK pathway

Chen

Sun

et al. 2018

J Cellular Molecular Medi

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Cervical cancer continues to be among the most frequent gynaecologic cancers worldwide. The phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) pathway is constitutively activated in cervical cancer. Inositol polyphosphate 4‐phosphatase type II (INPP4B) is a phosphoinositide phosphatase and considered a negative regulatory factor of the PI3K/AKT pathway. INPP4B has diverse roles in various tumours, but its role in cervical cancer is largely unknown. In this study, we investigated the role of INPP4B in cervical cancer. Overexpression of INPP4B in HeLa, SiHa and C33a cells inhibited cell proliferation, metastasis and invasiveness in CCK‐8, colony formation, anchorage‐independent growth in soft agar and Transwell assay. INPP4B reduced the expression of some essential proteins in the PI3K/AKT/SGK3 pathway including p‐AKT, p‐SGK3, p‐mTOR, phospho‐p70S6K and PDK1. In addition, overexpression of INPP4B decreased xenograft tumour growth in nude mice. Loss of INPP4B protein expression was found in more than 60% of human cervical carcinoma samples. In conclusion, INPP4B impedes the proliferation and invasiveness of cervical cancer cells by inhibiting the activation of two downstream molecules of the PI3K pathway, AKT and SGK3. INPP4B acts as a tumour suppressor in cervical cancer cells.

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Section: Discussionmentioning

confidence: 99%

INPP4B restrains cell proliferation and metastasis via regulation of the PI3K/AKT/SGK pathway

Chen

Sun

et al. 2018

J Cellular Molecular Medi

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“…INPP4B is a tumor suppressor in various types of cancers, while some studies have also indicated the oncogenic function of INPP4B in leukemia, breast cancer, and colon cancer [30]. Therefore, the role of INPP4B in tumor progression is controversial.…”

Section: Discussionmentioning

confidence: 99%

INPP4B reverses docetaxel resistance and epithelial-to-mesenchymal transition via the PI3K/Akt signaling pathway in prostate cancer

Chen

2016

Biochemical and Biophysical Research Communications

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“…The balance between PtdIns(3,4) P 2 and PtdIns(3,4,5) P 3 through the interplay between lipid kinases and phosphatases (Figure 1) is essential in regulating signaling pathways downstream of Akt [128]. The INPP4B phosphatase is acting as a tumor suppressor by dephosphorylating the 4’-position of PtdIns(3,4) P 2 and thus inhibiting the Akt signaling pathway [129]. …”

Section: Ptdins(34)p2 a Lipid Secondary Messengermentioning

confidence: 99%

Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways

Craene

Bertazzi

Bär

et al. 2017

IJMS

165

149

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Abstract:Phosphoinositides are lipids involved in the vesicular transport of proteins and lipids between the different compartments of eukaryotic cells. They act by recruiting and/or activating effector proteins and thus are involved in regulating various cellular functions, such as vesicular budding, membrane fusion and cytoskeleton dynamics. Although detected in small concentrations in membranes, their role is essential to cell function, since imbalance in their concentrations is a hallmark of many cancers. Their synthesis involves phosphorylating/dephosphorylating positions D3, D4 and/or D5 of their inositol ring by specific lipid kinases and phosphatases. This process is tightly regulated and specific to the different intracellular membranes. Most enzymes involved in phosphoinositide synthesis are conserved between yeast and human, and their loss of function leads to severe diseases (cancer, myopathy, neuropathy and ciliopathy).Keywords: lipids; membrane trafficking; vesicles; phosphoinositides; phosphatase; kinase Phosphoinositides in Cellular Membranes Lipids, Major Membrane ComponentsThe dynamic modulation of the physicochemical properties of membranes is required for eukaryotic cells function. Indeed, cells live in an environment characterized by temperature, relative humidity, pH, sun exposure, osmotic pressure and nutrient variations. Living organisms have to adapt to variations of these different factors in order to keep their intracellular balance. Eukaryotic cells have achieved this by adopting a compartmentalized organization, which minimizes the intracellular variations resulting from extracellular fluctuations. The plasma membrane is the first barrier separating the cytoplasm from the extracellular medium. Its composition ensures a mechanical protection, but also allows exchanges with the medium through transporters and receptors, as a form of very selective permeability.Membranes are composed of two phospholipid leaflets organized as a bilayer in which sterols, glycolipids and proteins are inserted. The phospholipids of this bilayer are amphiphilic with a hydrophilic group (head) linked to a hydrophobic group (tail) ( Figure 1A). In the bilayer, the hydrophobic groups face each other, thus creating a hydrophobic space in between them, which ensures its role as a barrier. This property is very important for the anchoring of hydrophobic molecules, such as sterols or ceramides, transmembrane domains or the lipid anchor of proteins. The lipid composition of membranes varies according to the organism (eukaryotes or prokaryotes), the cell type (among the different tissues of a multicellular organism), the membrane type (plasma Int.

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Phosphoinositide signaling in cancer: INPP4B Akt(s) out

Cited by 24 publications

References 10 publications

INPP4B restrains cell proliferation and metastasis via regulation of the PI3K/AKT/SGK pathway

INPP4B restrains cell proliferation and metastasis via regulation of the PI3K/AKT/SGK pathway

INPP4B reverses docetaxel resistance and epithelial-to-mesenchymal transition via the PI3K/Akt signaling pathway in prostate cancer

Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways

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