Is LKB1 a tumor suppressor?
Is LKB1 a tumor suppressor?
The liver kinase B1 (LKB1) is a serine/threonine kinase and tumor suppressor that couples bioenergetics to cell-growth control through regulation of mammalian target of rapamycin (mTOR) activity; however, the influence of LKB1 on tumor metabolism is not well defined.
What is the role of LKB1 AMPK in metabolic regulation?
LKB1/AMPK maintains cell polarity and inhibits cell proliferation and energy metabolism. Moreover, recent studies demonstrated that the LKB1/AMPK pathway plays an important role in the invasion and migration of tumor cells by regulating gene expression and activation of multiple signaling pathways.
What is LKB1 mutation?
Liver kinase B1 (LKB1, also known as STK11) was first identified as the causal mutation in Peutz–Jeghers Syndrome (PJS), a rare inherited autosomal dominant disorder characterised by the development of benign gastrointestinal hamartomas and the early onset of cancer (Hemminki et al, 1998).
What activates LKB1?
LKB1 activation is governed by a phosphorylation-independent allosteric mechanism in which it forms a heterotrimeric complex with 2 accessory proteins, STE20-related kinase adaptor (STRAD) and mouse protein 25 (MO25, also known as calcium binding protein 39, CAB39).
What is Peutz Jeghers syndrome?
Peutz-Jeghers syndrome (PJS) is an inherited condition that puts people at an increased risk for developing hamartomatous polyps in the digestive tract, as well as cancers of the breast, colon and rectum, pancreas, stomach, testicles, ovaries, lung, cervix, and other types listed below.
What does LKB1 stand for?
Serine/threonine kinase 11 (STK11) also known as liver kinase B1 (LKB1) or renal carcinoma antigen NY-REN-19 is a protein kinase that in humans is encoded by the STK11 gene.
How do you treat Peutz Jeghers syndrome?
Generally, polyps are treated with a procedure known as a polypectomy, which involves removing the polyps with an endoscope. If the polyps are very large, surgery may be necessary. Although there is no cure for PJS, treatment can reduce complications, such as abdominal pain, bowel obstruction, GI bleeding and cancer.
What are the symptoms of Peutz Jeghers syndrome?
What are the symptoms of Peutz-Jeghers syndrome (PJS)?
- Characteristic dark-colored spots (also called muco-cutaneous pigmentation) on various parts of the body.
- Development of hamartomatous polyps (non-cancerous overgrowths of tissue)
- Small bowel obstruction (blockage)
- Gastrointestinal bleeding.
- Stomach pain.
What is Peutz-Jeghers syndrome?
What causes Mitophagy?
Mitophagy is the selective degradation of mitochondria by autophagy. It often occurs to defective mitochondria following damage or stress.
What is the function of the STK11 / LKB1 gene?
The STK11/LKB1 gene, which encodes a member of the serine/threonine kinase family, regulates cell polarity and functions as a tumour suppressor. LKB1 is a primary upstream kinase of adenosine monophosphate-activated protein kinase ( AMPK ), a necessary element in cell metabolism that is required for maintaining energy homeostasis.
Is the LKB1 gene mutated in lung cancer?
However, the LKB1 gene was also found to be mutated in lung cancer of sporadic origin, predominantly adenocarcinomas. Further, more recent studies have uncovered a large number of somatic mutations of the LKB1 gene that are present in cervical, breast, intestinal, testicular, pancreatic and skin cancer.
How does testosterone affect the expression of LKB1?
Testosterone and DHT treatment of murine 3T3-L1 or human SGBS adipocytes for 24 h significantly decreased the mRNA expression of LKB1 via the androgen receptor and consequently reduced the activation of AMPK by phosphorylation. In contrast, 17β-estradiol treatment increased LKB1 mRNA, an effect mediated by oestrogen receptor alpha.
How is the LKB1-STRAD-MO25 heterotrimeric complex activated?
LKB1 is activated allosterically by binding to the pseudokinase STRAD and the adaptor protein MO25. The LKB1-STRAD-MO25 heterotrimeric complex represents the biologically active unit, that is capable of phosphorylating and activating AMPK and at least 12 other kinases that belong to the AMPK-related kinase family.