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expressed from independent transcripts indicating each snoRNA gene is potentially regulated in a spatial
and temporal pattern, and implies the regulatory mechanisms controlling a process such as RNA splicing is
highly cell-context specific . For instance, snoRNAU50 is responsible for methylating residue C248 on the
[108]
28S rRNA subunit, and has been further implicated in supporting a tumor-suppressor phenotype in breast
and prostate cancer . However, SNORD26 and SNORD30 are important regulators of rRNA processing,
[109]
and are expressed at higher abundance in metastatic prostate tumor samples, as compared to those having
low Gleason scores, presumably to support the increased demand for protein synthesis required during
tumorigenesis [17,110] . These studies support the notion that ncRNAs such as snoRNAs operate in a cell-context
dependent manner, and therefore the continued investigation of specific ncRNAs responsible for modulating
RNA splicing events, or the addition of RNA modifications that support a favorable cellular environment for
processes such as metastasis to occur, are important. Additional ncRNAs such as miRNAs also have a well
described role within the metastatic cascade yet are beyond the scope of this review. Herein, we highlight the
role lncRNAs play in promoting the metastatic cascade across a variety of cancer models [45,111,112] .

lncRNAs have been reported to control one of the most well described processes within the metastatic
cascade, namely the loss of E-cadherin expression on epithelial cells. Loss of E-cadherin expression is crucial
in ensuring proper epithelial cell-cell adhesion is maintained, as cell-cell connections are present so as to
support a state of quiescence within differentiated epithelial tissue . Evidence supporting this notion includes
[113]
studies assessing the mutational inactivation of E-cadherin or the elucidation of mechanisms underlying the
post-transcriptional repression of E-cadherin mRNA levels . Taken together, observations by numerous
[114]
investigators support a widely accepted hypothesis that loss of cellular polarity through the disruption of cell-
to-cell or cell-to-extracellular matrix (ECM) contacts is required for the initiation of metastasis.

Specific lncRNAs crucial in controlling E-cadherin abundance include FEZF1-AS1, which is found to
be dysregulated in non-small cell lung cancer (NSCLC) samples, as compared to adjacent normal tissue
samples . FEZF1-AS1 is also highly expressed in poorly differentiated tumor tissues as well from as those
[115]
of advanced tumor stage. FEZF1-AS1 abrogates the expression of E-cadherin by directly competing for
LSD1 binding, which disrupts the required association between E-cadherin and the LSD1/EZH2 complex
necessary for reducing turnover of the E-cadherin molecule itself. Therefore, lncRNAs operate not only
as sponges or decoys that modulate the RNA network within a cell, but also as disruptors of cytoplasmic
protein complexes essential in maintaining cellular polarity.

Another example of a lncRNA that regulates E-cadherin abundance includes lncRNA-ATB, which promotes
the invasion of colorectal cancer cells after TGF-β activation. This is a relevant mechanism to study, as
lncRNA-ATB harbors clinicopathologic significance, and correlates with tumor stage, as well as the presence
of metastatic foci within the sentinel lymph node and/or at distant organ sites. Furthermore, lncRNA-ATB
associates with reduced overall- and disease-free survival within colon cancer patients , and is elevated
[116]
in the serum of patients post-surgery, indicating lncRNAs are present in circulating biofluids and function
as biomarkers for tumor progression. Overall, with the advent of genome-wide transcriptomic studies,
consortiums such as ENCODE and TCGA have amassed a vast array of information that investigators
[27]
[117]
can utilize to elucidate how a particular lncRNA can modulate a series of RNA interaction networks
involved in the attenuation of metastatic phenotypes within a cell. Given this effort, there are a number of
newly identified lncRNAs strongly associated with metastasis that have the potential to be clinically relevant
readouts for this biological process. Here, we report on several lncRNAs that play an important role in the
metastatic process [118-120] .

The new linc’s on the block
Since 2012, the number of studies highlighting lncRNA involvement within the metastatic process has
increased nearly 20-fold to approximately 200 manuscripts being reported in Pubmed.gov this year. Half of