title: Deregulated ALG-2/HEBP2 axis alters microtubule dynamics and mitotic spindle behavior to stimulate cancer development.
abstract: Cancer cells are characterized by genomic instability, resulting in the accumulation of mutations that promote cancer progression. One way that genomic instability can arise is through improper regulation of the microtubule cytoskeleton that impacts the function of the mitotic spindle. In this study, we have identified a critical role for the interaction between apoptosis-linked gene 2 (ALG-2) and heme-binding protein 2 (HEBP2) in the above processes. Our data show that the gene copy numbers and mRNA levels for both ALG-2 and HEBP2 are significantly upregulated in breast and lung cancer. Coexpression of ALG-2 and HEBP2 markedly increases the cytoplasmic pool of ALG-2 and alters the subcellular distribution of HEBP2. Our data further reveal that abnormality in the ALG-2/HEBP2 interaction impairs spindle orientation and positioning during mitosis. In addition, this complex appears to modulate the dynamic properties of microtubules in cancer cells. These finding thus uncover an important function for deregulated ALG-2/HEBP2 axis in cancer development by influencing microtubule dynamics and spindle behavior, providing novel insight into the etiology and pathogenesis of cancer.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Yunqiang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Lyu
authors.affiliation: Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Sciences, Institute of Biomedical Sciences, Shandong Normal University, Jinan, Shandong, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Xinqi
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.|Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Sciences, Institute of Biomedical Sciences, Shandong Normal University, Jinan, Shandong, China.
authors.forename: Jun
authors.identifier: http://orcid.org/0000-0001-7858-8260
authors.initials: J
authors.lastname: Zhou
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D000081062:Heme-Binding Proteins; D006420:Hemeproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008870:Microtubules / Q000378:metabolism* / Q000473:pathology; D008938:Mitosis; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; C516258:HEBP2 protein, human; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; C097753:PDCD6 protein, human; D011257:Pregnancy Proteins; D012333:RNA, Messenger
keywords: ALG-2; HEBP2; cancer; microtubule; mitotic spindle