PMID- 29290996 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 63 DP - 2017 Dec 5 TI - The role of talin2 in breast cancer tumorigenesis and metastasis. PG - 106876-106887 LID - 10.18632/oncotarget.22449 [doi] AB - Recent studies show that talin2 has a higher affinity to beta-integrin tails and is indispensable for traction force generation and cell invasion. However, its roles in cell migration, cancer cell metastasis and tumorigenesis remain to be determined. Here, we used MDA-MB-231 human breast cancer cells as a model to define the roles of talin2 in cell migration, invasion, metastasis and tumorigenesis. We show here that talin2 knockdown (KD) inhibited cell migration and focal adhesion dynamics, a key step in cell migration, and that talin2 knockout (KO) inhibited cell invasion and traction force generation, the latter is crucial for cell invasion. Re-expression of talin2(WT) in talin2-KO cells restored traction force generation and cell invasion, but that of talin2(S339C), a beta-integrin-binding deficient mutant, did not. Moreover, talin2 KO (or KD) suppressed tumorigenesis and metastasis in mouse xenograft models. However, surprisingly, re-expression of talin2(WT) in talin2-KO cells did not rescue tumorigenesis. Thus, talin2 is required for breast cancer cell migration, invasion, metastasis and tumorigenesis, although exogenous expression of high levels of talin2 could inhibit tumorigenesis. FAU - Li, Liqing AU - Li L AD - Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA. FAU - Li, Xiang AU - Li X AD - Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA. FAU - Qi, Lei AU - Qi L AD - Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA. FAU - Rychahou, Piotr AU - Rychahou P AD - Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA. FAU - Jafari, Naser AU - Jafari N AD - Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA. FAU - Huang, Cai AU - Huang C AD - Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA. AD - Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40506, USA. LA - eng GR - P30 CA177558/CA/NCI NIH HHS/United States GR - R01 CA195573/CA/NCI NIH HHS/United States GR - R01 GM122994/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20171106 PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 PMC - PMC5739781 OTO - NOTNLM OT - cell migration OT - invasion OT - metastasis OT - talin2 OT - tumor growth COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest to disclose. EDAT- 2018/01/02 06:00 MHDA- 2018/01/02 06:01 PMCR- 2017/12/05 CRDT- 2018/01/02 06:00 PHST- 2017/08/06 00:00 [received] PHST- 2017/10/25 00:00 [accepted] PHST- 2018/01/02 06:00 [entrez] PHST- 2018/01/02 06:00 [pubmed] PHST- 2018/01/02 06:01 [medline] PHST- 2017/12/05 00:00 [pmc-release] AID - 22449 [pii] AID - 10.18632/oncotarget.22449 [doi] PST - epublish SO - Oncotarget. 2017 Nov 6;8(63):106876-106887. doi: 10.18632/oncotarget.22449. eCollection 2017 Dec 5.