LBK1, A CONFUSING MARKER OF CANCER
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In lung cancer, Harvard researchers have pushed us now to request a lengthy list of Markers in order to direct our treatment.  The many options of therapeutic interventions have to be selected more sharply as new Driver mutations are discovered and new Target therapy drugs are made available.  We made a summary of drugs and their relevant Driver Mutations in our previous blog. (KRAS, EGFR, ALK, HER-2, BRAF, ROS-1,RET, MEK-1,NRAS, MET etc. for Driver Mutations.....Medications included Erlotinib, Gefitinib, Herceptin, Lapatinib, Veramufenib, Cabozantinib, Crizotinib etc. - SEE OUR BLOG)

But for a while, 5 Mutations were mostly adopted: KRAS, BRAF, EGFR, ALK and LBK1.
The surprise choice of LBK1 has remained somewhat of a confusion. Because no one knows what to do with the information despite the fact that we know a bit about the gene.  In these days, any Mutation or suppressed gene is suspect and prognosis conclusions are down. Presence of Mutation at LBK1 is considered of poor prognosis.  But wait a second! Let me shake a bit this notion:

Where do we find LBK1 alteration?

In DCIS
and In Polyps
and in Hamartomas ( Peutz Jeggers) : These do not sound like invasive cancers to me!

The DCIS case: Clinicians have maintained that DCIS do not invade, and Lymph node biopsy is generally not performed in case of DCIS.  Malignant transformation occurs here at 1% a year.  So we need additional Mutations for DCIS to adopt a cancerous profile.

In Peuts Jeggers, despite the presence of LBK1 (STK-1), polyps take their time to transform.  There the patient could develop pancreatic cancers for sure, but only after additional mutated genes come to bear! And the likelihood of this is high since a number of known substrates have been recognized to interact with LBK1.

Through Wikipedia:

SUBSTRATES OF LBK1 INCLUDE:

1.   BRSK 1&2 --------Through these substrate, it insure Neuronal Polarity.  And control length of neurons.
                       I should come to cellular polarity in a bit!  But here also comes its power to organize Microtubules and could have implications on resistance vs sensitivity to Taxanes!

2.  MARK 1&2--------This is where it controls Apico-basal cell Polarity, it may be controlling the      popular topic of Flippase, Floppase and Scramblase.

3.  SIK 1,2 : Through this substrate and its co-activator TORC2, LBK1 finds its inhibitory effect on Gluconeogesis.

4. AMPK signal pathways which favor proteins formation and translation while blocking lipogenesis.  Metabolically, it favors Catalysis with generation of ATP while blocking reactions requiring consumption of ATP.  At the cellular membrane the exchange of phosphorylated groups drive GTPase.  Putting LBK1 center to pathways activation.  At the Mitochondrial Membrane this has even more of an impact.

5.  NUAK  1,&2  which regulate Apoptosis through P53.  It is speculated that the overall effect of LBK1 is naturally anti-tumor.  Its alteration stops Apoptosis.

6. In the Embryo, LBK1 has demonstrated a role in Angiogenesis.   MEK or VEGF interaction is assumed.

One speculated that chronic exposure to Insulin like growth factor stimulation, or Estrogenic stimulation or inflammation or chronic mechanical stimulation forces desensitization through SPRADD or other genes altering LBK1 leading to loss of polarity and linear arrangement of cells by dysfunctional adhesion leading to "benign tumorous formations called polyps.  Further alterations happen as abnormal genetic evolution occurs and progresses into a full blown Malignancy.

It is also believed that once malignant transformation happens, LBK1 functions could "amplify" then the transformation favoring cell migration.

Many questions remain to be solved when it comes to LBK1...