title: Par3L enhances colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway.
abstract: Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells. Consistent with previous studies, we showed that Par3L interacts with a tumor suppressor protein liver kinase B1 (Lkb1). Moreover, Par3L depletion resulted in abnormal activation of Lkb1/AMPK signaling cascade. Knockdown of Lkb1 in these cells could significantly reduce AMPK activity and partially rescue cell death caused by Par3L knockdown. Furthermore, we showed that Par3L KO cells were more sensitive to chemotherapies and irradiation. Together, these results suggest that Par3L is essential for colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway, and is a putative therapeutic target for CRC.
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Jiangxi Province, China.
authors.forename: Taiyuan
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Jiangxi Province, China.
authors.forename: Dongning
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Jiangxi Province, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Lei
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Jiangxi Province, China. Electronic address: JiangQG168@gmail.com.
authors.forename: Qunguang
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017209:Apoptosis; D001483:Base Sequence; D064113:CRISPR-Cas Systems; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D000072669:Gene Editing; D055786:Gene Knockout Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C471157:PARD3B protein, human; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK pathway; CRISPR/Cas; Colorectal cancer; Lkb1; Par3L