title: Phosphorylation of caspase-7 by p21-activated protein kinase (PAK) 2 inhibits chemotherapeutic drug-induced apoptosis of breast cancer cell lines.
abstract: p21-activated kinase (PAK) 2, a member of the PAK family of serine/threonine protein kinases, plays an important role in physiological processes such as motility, survival, mitosis, and apoptosis. However, the role of PAK2 in resistance to chemotherapy is unclear. Here we report that PAK2 is highly expressed in human breast cancer cell lines and human breast invasive carcinoma tissue compared with a human non-tumorigenic mammary epithelial cell line and adjacent normal breast tissue, respectively. Interestingly, we found that PAK2 can bind with caspase-7 and phosphorylate caspase-7 at the Ser-30, Thr-173, and Ser-239 sites. Functionally, the phosphorylation of caspase-7 decreases its activity, thereby inhibiting cellular apoptosis. Our data indicate that highly expressed PAK2 mediates chemotherapeutic resistance in human breast invasive ductal carcinoma by negatively regulating caspase-7 activity.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Weihong
authors.initials: W
authors.lastname: Wen
authors.forename: Kangdong
authors.initials: K
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Margarita
authors.initials: M
authors.lastname: Malakhova
authors.forename: Cong
authors.initials: C
authors.lastname: Peng
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.forename: Hong-Gyum
authors.initials: HG
authors.lastname: Kim
authors.forename: Weiya
authors.initials: W
authors.lastname: Ma
authors.forename: Yong Yeon
authors.initials: YY
authors.lastname: Cho
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Ziming
authors.initials: Z
authors.lastname: Dong
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D044584:Carcinoma, Ductal / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D053179:Caspase 7 / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport; D054462:p21-Activated Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D054462:p21-Activated Kinases; D053179:Caspase 7