LKB1 and AMPK maintain epithelial cell polarity under energetic stress

Mirouse, Vincent; Swick, Lance L.; Kazgan, Nevzat; Johnston, Daniel St; Brenman, Jay E.

doi:10.1083/jcb.20070205310112013r

Cited by 35 publications

(44 citation statements)

References 2 publications

(3 reference statements)

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“…The mammalian homolog of Drosophila, Par-4, is a serine-threonine kinase Lkb1 (liver kinase B1, STK11), which has been implicated in both regulation of epithelial integrity and tumor progression (14). In Drosophila oocytes, Lkb1/ Par-4 participates in the formation of anterior-posterior axis and apicobasal polarity (15), whereas loss of Lkb1/Par-4 or its downstream target AMPK-α in follicle cells leads to polarity defects and increased proliferation, especially under energetic stress (16). In mammals, forced Lkb1 activity is sufficient to induce polarization of single intestinal epithelial cells (17), and in murine pancreatic acini, loss of Lkb1 leads to cell polarity defects in conjunction with formation of cystic neoplasms (18).…”

mentioning

confidence: 99%

Tumor suppressor function of Liver kinase B1 (Lkb1) is linked to regulation of epithelial integrity

Partanen

Tervonen

Myllynen

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

110

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Although loss of epithelial integrity is a hallmark of advanced cancer, it remains poorly understood whether genetic alterations corrupting this integrity causally facilitate tumorigenesis. We show that conditional deletion of tumor suppressor gene Lkb1 (Par-4) in the mammary gland compromises epithelial integrity manifested by mislocalization of cell polarity markers, lateralization of tight junctions, deterioration of desmosomes and basement membrane (BM), and hyperbranching of the mammary ductal tree. We identify the desmosomal BM remodelling serine protease Hepsin as a key factor mediating Lkb1 loss-induced structural alterations in mammary epithelium and BM fragmentation. Although loss of Lkb1 alone does not promote mammary tumorigenesis, combination of Lkb1 deficiency with oncogenic c-Myc leads to dramatic acceleration in tumor formation. The results coupling Lkb1 loss-mediated epithelial integrity defects to mislocalization of serine protease Hepsin and to oncogenic synergy with c-Myc imply that Lkb1 loss facilitates oncogenic proliferation by releasing epithelial cells from structural BM boundaries.breast cancer | mouse model

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mentioning

confidence: 99%

Tumor suppressor function of Liver kinase B1 (Lkb1) is linked to regulation of epithelial integrity

Partanen

Tervonen

Myllynen

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

110

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“…It is activated during starvation. Previous studies have shown that AMPKα mutation could cause epithelial disruption and proliferation in the follicle cells but only under energy stress (Mirouse et al 2007). Since loss of awd results in delocalization of adherens junction and breakdown of epithelial characteristics (Woolworth et al 2009), the AMPK-awd axis may the key component in the regulation of nutrientdependent epithelial integrity.…”

Section: Drosophila Melanogastermentioning

confidence: 99%

Progress on Nme (NDP kinase/Nm23/Awd) gene family-related functions derived from animal model systems: studies on development, cardiovascular disease, and cancer metastasis exemplified

Hsu

Steeg

Zollo

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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“…It is well known that LKB1 controls cell polarity and maintains intracellular energy balance (8,9). LKB1 functions as a tumor suppressor by phosphorylating and activating AMP-activated protein kinase (AMPK) (8,9).…”

Section: The Function Of Liver Kinase B1mentioning

confidence: 99%

“…LKB1 functions as a tumor suppressor by phosphorylating and activating AMP-activated protein kinase (AMPK) (8,9). LKB1/AMPK signaling regulates the formation of cytoskeletal microtubules and the expression of cell polarity proteins, including prostate apoptosis response-4 (PAR-4), to maintain cell polarity (10).…”

Section: The Function Of Liver Kinase B1mentioning

confidence: 99%

Role of the LKB1/AMPK pathway in tumor invasion and metastasis of cancer cells (Review)

Huang

Lü

et al. 2015

Oncology Reports

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Abstract. Liver kinase B1 (LKB1), also known as serine/threo nine kinase 11 (STK11), is a tumor suppressor that is inactivated in Peutz-Jeghers familial cancer syndrome. LKB1 phosphorylates and activates AMP-activated protein kinase (AMPK), which negatively regulates cancer cell proliferation and metabolism. However, recent evidence demonstrates that the LKB1/AMPK pathway is involved in the process of tumor invasion and migration, which is an important hallmark of carcinoma progression to higher pathological grades of malignancy. This review focuses on the function of the LKB1/AMPK pathway in the invasion and migration of cancer cells and provides an overview of therapeutic strategies aimed at this pathway in malignant tumors.

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LKB1 and AMPK maintain epithelial cell polarity under energetic stress

Cited by 35 publications

References 2 publications

Tumor suppressor function of Liver kinase B1 (Lkb1) is linked to regulation of epithelial integrity

Tumor suppressor function of Liver kinase B1 (Lkb1) is linked to regulation of epithelial integrity

Progress on Nme (NDP kinase/Nm23/Awd) gene family-related functions derived from animal model systems: studies on development, cardiovascular disease, and cancer metastasis exemplified

Role of the LKB1/AMPK pathway in tumor invasion and metastasis of cancer cells (Review)

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