RalBP1 Is Necessary for Metastasis of Human Cancer Cell Lines

Wu, Zhisheng; Owens, Charles; Chandra, Nidhi; Popovic, Kay; Conaway, Mark; Theodorescu, Dan

doi:10.1593/neo.101080

Cited by 59 publications

(43 citation statements)

References 22 publications

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“…In this way, RALBP1 is important for actin dynamics, filopodia formation and membrane ruffling [1,26,27] , thereby contributing to cancer cell adhesion, invasion and migration. RALBP1 is critical for the migration of bladder and prostate cancer cells, which is partly independent of its interaction with RAL [28] . RALBP1 is also important for endocytosis, including receptormediated endocytosis of proteins such as epidermal growth factor receptor, insulin receptor and transferrin receptor, through its interactions with POB1, Reps1 and AP2 [29][30][31] .…”

Section: Ras Mutation and Cancer Therapeuticsmentioning

confidence: 99%

“…Both RAL isoforms have important functions in the growth and metastasis of bladder cancer [28,64,65] . RALA is important for the progression of hepatocellular carcinoma, colorectal cancer, chronic myeloid leukemia, squamous cell carcinoma of the skin and nerve sheath tumors [57,[66][67][68][69] .…”

Section: Ral In Cancermentioning

confidence: 99%

“…RALA is important for the progression of hepatocellular carcinoma, colorectal cancer, chronic myeloid leukemia, squamous cell carcinoma of the skin and nerve sheath tumors [57,[66][67][68][69] . RALA is also promigratory, assisting in the metastasis of prostate cancer to bone and aiding in the invasion of squamous cell carcinoma of the skin and renal cancers [28,68,70,71] . RALB, however, is important for the invasion and migration of bladder cancer, oral squamous cell carcinoma, B cells and multiple myeloma cells [53,72,73] .…”

Section: Ral In Cancermentioning

confidence: 99%

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The RAS-RAL axis in cancer: evidence for mutation-specific selectivity in non-small cell lung cancer

Guin

Theodorescu

2015

Acta Pharmacol Sin

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Activating RAS mutations are common in human tumors. These mutations are often markers for resistance to therapy and subsequent poor prognosis. So far, targeting the RAF-MEK-ERK and PI3K-AKT signaling pathways downstream of RAS is the only promising approach in the treatment of cancer patients harboring RAS mutations. RAL GTPase, another downstream effector of RAS, is also considered as a therapeutic option for the treatment of RAS-mutant cancers. The RAL GTPase family comprises RALA and RALB, which can have either divergent or similar functions in different tumor models. Recent studies on non-small cell lung cancer (NSCLC) have showed that different RAS mutations selectively activate specific effector pathways. This observation requires broader validation in other tumor tissue types, but if true, will provide a new approach to the treatment of RAS-mutant cancer patients by targeting specific downstream RAS effectors according to the type of RAS mutation. It also suggests that RAL GTPase inhibition will be an important treatment strategy for tumors harboring RAS glycine to cysteine (G12C) or glycien to valine (G12V) mutations, which are commonly found in NSCLC and pancreatic cancer. Review RAS GTPase overviewRAS is the most extensively studied GTPase [1] . It is known to regulate various cellular functions, including proliferation, survival, growth, migration, differentiation and cytoskeletal dynamics [2][3][4] (Figure 1). Not coincidentally, increased activities of all of these processes are required by tumor cells to promote tumor growth. Activating oncogenic RAS mutations lead to treatment resistance in various tumor models and poor patient outcomes [3,[5][6][7][8][9] . Three human RAS genes have been identified: HRAS, KRAS, and NRAS [1,2] . These encode the related proteins HRAS, KRAS and NRAS, respectively, of 189 amino acids in length [1,4] . KRAS exists as two isoforms, 4A and 4B, which are generated by alternative exon splicing [10] . These different RAS genes are well known to have differential cellular specificities and intrinsic transforming potentials [3,4,10] .In normal cells, RAS proteins act as molecular switches for critical cellular functions. RAS proteins are activated by upstream receptors such as receptor tyrosine kinases * To whom correspondence should be addressed. E-mail dan.theodorescu@ucdenver.edu Received 2014-08-07 Accepted 2014-10-30 Figure 1. RAS GTPase activation and downstream signaling. The cartoon shows the mechanism of RAS GTPase activation by upstream stimuli and numerous downstream effectors stimulated by activated RAS. RAS regulates critical cellular functions through these effectors. Constitutive RAS activation due to mutations leads to protumorigenic signaling through these effectors.

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Section: Ras Mutation and Cancer Therapeuticsmentioning

confidence: 99%

Section: Ral In Cancermentioning

confidence: 99%

Section: Ral In Cancermentioning

confidence: 99%

See 1 more Smart Citation

The RAS-RAL axis in cancer: evidence for mutation-specific selectivity in non-small cell lung cancer

Guin

Theodorescu

2015

Acta Pharmacol Sin

Self Cite

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“…Therefore, models of orthotopic growth are more appropriate for studies related to metastasis dissemination or response to any treatment. There are some heterotopic models such as inoculation into the tail vein or the left ventricle of the heart which have been widely used to evaluate the process of extravasations and colonization in the lung or bone, respectively (Growcott, 2009;Wu et al, 2010). Although very used, these models consider only a limited aspect of the metastatic process (Figure 3).…”

Section: Heterotopic Tumor Growthmentioning

confidence: 99%

Animal Models for Basic and Preclinical Research in Bladder Cancer

Eiján¹,

Lodillinsky²,

Sandes³

2012

Bladder Cancer - From Basic Science to Robotic Surgery

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“…Phosphorylation of constitutively active RalA (RalA G23V ) at a conserved C-terminal S194 residue, by Aurora A kinase, promotes collagenI-induced cell motility and anchorage-independent growth in MDCK epithelial cells (J. C. . This phosphorylation caused RalA relocation from the plasma membrane to endomembranes, where RalA associated preferentially with its effector Ral binding protein 1 RalBP1/RLIP76, thereby promoting cell motility during human cancer cell metastasis (Lim, et al, 2010;Z. Wu, et al, 2010).…”

Section: Phospho-regulation Of Small Gtpases Their Effectors and Regmentioning

confidence: 99%