title: MIG-10 (Lamellipodin) stabilizes invading cell adhesion to basement membrane and is a negative transcriptional target of EGL-43 in C. elegans.
abstract: Cell invasion through basement membrane (BM) occurs in many physiological and pathological contexts. MIG-10, the Caenorhabditis elegans Lamellipodin (Lpd), regulates diverse biological processes. Its function and regulation in cell invasive behavior remain unclear. Using anchor cell (AC) invasion in C. elegans as an in vivo invasion model, we have previously found that mig-10's activity is largely outside of UNC-6 (netrin) signaling, a chemical cue directing AC invasion. We have shown that MIG-10 is a target of the transcription factor FOS-1A and facilitates BM breaching. Combining genetics and imaging analyses, we report that MIG-10 synergizes with UNC-6 to promote AC attachment to the BM, revealing a functional role for MIG-10 in stabilizing AC-BM adhesion. MIG-10 is also required for F-actin accumulation in the absence of UNC-6. Further, we identify mig-10 as a transcriptional target negatively regulated by EGL-43A (C. elegans Evi-1 proto-oncogene), a transcription factor positively controlled by FOS-1A. The revelation of this negative regulation unmasks an incoherent feedforward circuit existing among fos-1, egl-43 and mig-10. Moreover, our study suggests the functional importance of the negative regulation on mig-10 expression by showing that excessive MIG-10 impairs AC invasion. Thus, we provide new insight into MIG-10's function and its complex transcriptional regulation during cell invasive behavior.
authors.affiliation: Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Shen
authors.affiliation: Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Lei
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: David
authors.initials: D
authors.lastname: Matus
authors.affiliation: Department of Biology, Duke University, 124 Science Drive, Box 90388, Durham, NC 27708, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sherwood
authors.affiliation: Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China; Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. Electronic address: wzwangzheng@gmail.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D012734:Disorders of Sex Development / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006066:Gonads / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000075385:Netrins; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000199:Actins; D029742:Caenorhabditis elegans Proteins; C084226:Egl-43 protein, C elegans; C520083:FOS-1 protein, C elegans; C105812:Mig-10 protein, C elegans; D009419:Nerve Tissue Proteins; D000075385:Netrins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; C078146:UNC-6 protein, C elegans
keywords: Anchor cell; Cell invasion; EGL-43; Lamellipodin; MIG-10