2016
DOI: 10.1091/mbc.e15-08-0569
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LKB1 kinase-dependent and -independent defects disrupt polarity and adhesion signaling to drive collagen remodeling during invasion

Abstract: Farnesylation of the LKB1 C-terminal domain promotes mesenchymal polarization and directional persistence during three-dimensional invasion by activating the Rho-GTPase RhoA in a kinase-independent manner. Conversely, LKB1 kinase activity represses FAK activity through MARK1, which subsequently inhibits downstream collagen remodeling during invasion.

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Cited by 32 publications
(63 citation statements)
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“…We use two different non-small cell lung cancer (NSCLC) cell lines (H1299, H157) with various perturbations to liver kinase B1 (LKB1) and microtubule affinity regulating kinase 1 (MARK1) pathways232526 to demonstrate the discriminatory power of the local alignment vector measure. Liver kinase B1 (LKB1), also known as a serine-threonine kinase (STK11), is a tumor suppressor262728.…”
Section: Resultsmentioning
confidence: 99%
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“…We use two different non-small cell lung cancer (NSCLC) cell lines (H1299, H157) with various perturbations to liver kinase B1 (LKB1) and microtubule affinity regulating kinase 1 (MARK1) pathways232526 to demonstrate the discriminatory power of the local alignment vector measure. Liver kinase B1 (LKB1), also known as a serine-threonine kinase (STK11), is a tumor suppressor262728.…”
Section: Resultsmentioning
confidence: 99%
“…LKB1 directly phosphorylates and activates AMP-activated protein kinase (AMPK), and its family member MARK1252635. MARK1 goes on to inhibits focal adhesion kinase (FAK) to regulate collagen remodeling and cancer cell motility233637. Therefore, LKB1 is the upstream regulator of AMPK and MARK1, and play a key role in cancer cell invasion and ECM remodeling and realignment.…”
Section: Resultsmentioning
confidence: 99%
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“…During invasion, Lkb1-null spheroids exhibit increased collagen alignment compared with LKB1 WT spheroids ( Figure 2, D and E). We tested the requirement for FAK activity by treating Lkb1-null spheroids with the FAK inhibitor PF-562271 and implemented a local alignment coefficient to quantify the effect ( Figure 2, E and F) (18). Our results indicate that Lkb1-null spheroids are indeed dependent on FAK activity to align collagen fibers during collective 3D invasion.…”
Section: A Lenti-mentioning
confidence: 93%
“…FAK is a nonreceptor tyrosine kinase that serves as a master regulator of cell adhesion during cell motility and has kinase-dependent roles in cell invasion (18). As such, several anticancer agents targeting FAK activity are in clinical development (19).…”
Section: Introductionmentioning
confidence: 99%