PMID- 35762511 OWN - NLM STAT- MEDLINE DCOM- 20220629 LR - 20220906 IS - 1477-9137 (Electronic) IS - 0021-9533 (Linking) VI - 135 IP - 12 DP - 2022 Jun 15 TI - Syntaxin 7 contributes to breast cancer cell invasion by promoting invadopodia formation. LID - jcs259576 [pii] LID - 10.1242/jcs.259576 [doi] AB - Invasion in various cancer cells requires coordinated delivery of signaling proteins, adhesion proteins, actin-remodeling proteins and proteases to matrix-degrading structures called invadopodia. Vesicular trafficking involving SNAREs plays a crucial role in the delivery of cargo to the target membrane. Screening of 13 SNAREs from the endocytic and recycling route using a gene silencing approach coupled with functional assays identified syntaxin 7 (STX7) as an important player in MDA-MB-231 cell invasion. Total internal reflection fluorescence microscopy (TIRF-M) studies revealed that STX7 resides near invadopodia and co-traffics with MT1-MMP (also known as MMP14), indicating a possible role for this SNARE in protease trafficking. STX7 depletion reduced the number of invadopodia and their associated degradative activity. Immunoprecipitation studies revealed that STX7 forms distinct SNARE complexes with VAMP2, VAMP3, VAMP7, STX4 and SNAP23. Depletion of VAMP2, VAMP3 or STX4 abrogated invadopodia formation, phenocopying what was seen upon lack of STX7. Whereas depletion of STX4 reduced MT1-MMP level at the cell surfaces, STX7 silencing significantly reduced the invadopodia-associated MT1-MMP pool and increased the non-invadosomal pool. This study highlights STX7 as a major contributor towards the invadopodia formation during cancer cell invasion. This article has an associated First Person interview with the first author of the paper. CI - (c) 2022. Published by The Company of Biologists Ltd. FAU - Parveen, Sameena AU - Parveen S AUID- ORCID: 0000-0002-9181-8283 AD - Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Bhopal 462066, India. FAU - Khamari, Amrita AU - Khamari A AUID- ORCID: 0000-0003-3454-2759 AD - Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Bhopal 462066, India. FAU - Raju, Jyothikamala AU - Raju J AUID- ORCID: 0000-0001-9444-6211 AD - Thazhathemalayil House, Thodupuzha East PO, Keerikode, Kerala 685585, India. FAU - Coppolino, Marc G AU - Coppolino MG AUID- ORCID: 0000-0002-4538-7929 AD - Department of Molecular and Cellular Biology, University of Guelph, Ontario N1G 2W1, Canada. FAU - Datta, Sunando AU - Datta S AUID- ORCID: 0000-0002-1417-0276 AD - Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Bhopal 462066, India. LA - eng GR - MHRD/BIO/2019047/Ministry of Human Resources and Development, India/ GR - CRG/2019/004580/Science and Engineering Research Board/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220628 PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 0 (Qa-SNARE Proteins) RN - 0 (SNARE Proteins) RN - 0 (Vesicle-Associated Membrane Protein 2) RN - 0 (Vesicle-Associated Membrane Protein 3) RN - EC 3.4.24.80 (Matrix Metalloproteinase 14) SB - IM MH - *Breast Neoplasms/genetics/metabolism MH - Female MH - Humans MH - Matrix Metalloproteinase 14/genetics/metabolism MH - Neoplasm Invasiveness MH - *Podosomes/metabolism MH - Protein Transport MH - *Qa-SNARE Proteins/genetics/metabolism MH - SNARE Proteins/metabolism MH - Vesicle-Associated Membrane Protein 2/genetics/metabolism MH - Vesicle-Associated Membrane Protein 3/metabolism OTO - NOTNLM OT - Cortactin OT - Invadopodia OT - MT1-MMP OT - SNAREs OT - STX4 OT - STX7 OT - Tks5 OT - VAMP2 OT - VAMP3 COIS- Competing interests The authors declare no competing or financial interests. EDAT- 2022/06/29 06:00 MHDA- 2022/06/30 06:00 CRDT- 2022/06/28 07:12 PHST- 2021/11/12 00:00 [received] PHST- 2022/05/12 00:00 [accepted] PHST- 2022/06/28 07:12 [entrez] PHST- 2022/06/29 06:00 [pubmed] PHST- 2022/06/30 06:00 [medline] AID - 275829 [pii] AID - 10.1242/jcs.259576 [doi] PST - ppublish SO - J Cell Sci. 2022 Jun 15;135(12):jcs259576. doi: 10.1242/jcs.259576. Epub 2022 Jun 28.