2014
DOI: 10.18632/oncotarget.1904
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Nuclear HER4 mediates acquired resistance to trastuzumab and is associated with poor outcome in HER2 positive breast cancer

Abstract: The role of HER4 in breast cancer is controversial and its role in relation to trastuzumab resistance remains unclear. We showed that trastuzumab treatment and its acquired resistance induced HER4 upregulation, cleavage and nuclear translocation. However, knockdown of HER4 by specific siRNAs increased trastuzumab sensitivity and reversed its resistance in HER2 positive breast cancer cells. Preventing HER4 cleavage by a γ-secretase inhibitor and inhibiting HER4 tyrosine kinase activity by neratinib decreased tr… Show more

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Cited by 58 publications
(49 citation statements)
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“…43,44 Moreover, it has been considered to mediate acquired resistance to chemotherapy. 36 Consistently, we found that inhibition of ERBB4 enhanced colon cancer cells apoptosis in response to L-OHP. In addition, Linc00152 play an important role in L-OHP resistance by acting as a ceRNA.…”
Section: Discussionsupporting
confidence: 75%
See 1 more Smart Citation
“…43,44 Moreover, it has been considered to mediate acquired resistance to chemotherapy. 36 Consistently, we found that inhibition of ERBB4 enhanced colon cancer cells apoptosis in response to L-OHP. In addition, Linc00152 play an important role in L-OHP resistance by acting as a ceRNA.…”
Section: Discussionsupporting
confidence: 75%
“…As ERBB4 overexpression is associated with chemoresistance, 36 to investigate whether Linc00152 confers L-OHP resistance by modulating ERBB4, we first examined the effect of ERBB4 on cell response to L-OHP. Knockdown of ERBB4 reduced cell viability (Figure 4a,b), and increased apoptosis (Figure 4c,d) following 10µmol/l L-OHP treatment for 72 hours compared with control cells.…”
Section: Linc00152 Mediates Drug Resistance Through Sponging Mir-193amentioning
confidence: 99%
“…Because of lapatinib's dual EGFR and HER2 inhibition, in contrast to the effects on trastuzumab therapy, increased copy number of EGFR has been linked to lapatinib sensitivity in breast cancer [137]. HER4 has also been demonstrated in vitro to be upregulated with acquisition of trastuzumab resistance, which can be reversed with anti-HER4 therapies [138]. Clinically, however, the results challenge these in vitro findings.Two studies demonstrated increased response to trastuzumab and improved clinical outcomes in patients with tumors high in HER4, and another study showed no relationship of HER4 to clinical response [139][140][141].…”
Section: Signaling Through Alternate Her Family Proteinsmentioning
confidence: 99%
“…There are potentially oncogenic ERBB4 mutations in non-small cell lung cancer (9), and it has been reported that HER4 is overexpressed in human colon cancer and enhances cellular transformation (10). In addition, HER4 promotes breast cancer cell proliferation, mediates acquired resistance to ERBB2 inhibitors and may serve as a prognostic marker in patients with breast cancer (11)(12)(13)(14). However, the role of HER4 in CRC remains to be fully elucidated.…”
Section: Introductionmentioning
confidence: 99%