Angio-associated migratory cell protein interacts with epidermal growth factor receptor and enhances proliferation and drug resistance in human non-small cell lung cancer cells

Yao, Shun; Shi, Feifei; Wang, Yingying; Sun, Xiaoyang; Sun, Wenbo; Zhang, Yifeng; Liu, Xiangguo; Su, Ling

doi:10.1016/j.cellsig.2019.05.004

Cited by 10 publications

(9 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CCND1 encodes the cyclin D1 protein, which is complexed with cyclin-dependent kinases (CDKs) and regulates the cell cycle to induce cell migration and angiogenesis, linked to melanoma and metastatic progression [39,40]. AAMP (angio-associated migratory cell protein) belongs to the immunoglobulin superfamily and has a function in cell migration and angiogenesis in breast cancer and non-small cell lung cancer [41,42].…”

Section: Association Of Baseline Gene Expression With Pathologic Respmentioning

confidence: 99%

CTLA-4 blockade and interferon-α induce proinflammatory transcriptional changes in the tumor immune landscape that correlate with pathologic response in melanoma

et al. 2021

View full text Add to dashboard Cite

Patients with locally/regionally advanced melanoma were treated with neoadjuvant combination immunotherapy with high-dose interferon α-2b (HDI) and ipilimumab in a phase I clinical trial. Tumor specimens were obtained prior to the initiation of neoadjuvant therapy, at the time of surgery and progression if available. In this study, gene expression profiles of tumor specimens (N = 27) were investigated using the NanoString nCounter® platform to evaluate associations with clinical outcomes (pathologic response, radiologic response, relapse-free survival (RFS), and overall survival (OS)) and define biomarkers associated with tumor response. The Tumor Inflammation Signature (TIS), an 18-gene signature that enriches for response to Programmed cell death protein 1 (PD-1) checkpoint blockade, was also evaluated for association with clinical response and survival. It was observed that neoadjuvant ipilimumab-HDI therapy demonstrated an upregulation of immune-related genes, chemokines, and transcription regulator genes involved in immune cell activation, function, or cell proliferation. Importantly, increased expression of baseline pro-inflammatory genes CCL19, CD3D, CD8A, CD22, LY9, IL12RB1, C1S, C7, AMICA1, TIAM1, TIGIT, THY1 was associated with longer OS (p < 0.05). In addition, multiple genes that encode a component or a regulator of the extracellular matrix such as MMP2 and COL1A2 were identified post-treatment as being associated with longer RFS and OS. In all baseline tissues, high TIS scores were associated with longer OS (p = 0.0166). Also, downregulated expression of cell proliferation-related genes such as CUL1, CCND1 and AAMP at baseline was associated with pathological and radiological response (unadjusted p < 0.01). In conclusion, we identified numerous genes that play roles in multiple biological pathways involved in immune activation, immune suppression and cell proliferation correlating with pathological/radiological responses following neoadjuvant immunotherapy highlighting the complexity of immune responses modulated by immunotherapy. Our observations suggest that TIS may be a useful biomarker for predicting survival outcomes with combination immunotherapy.

show abstract

Section: Association Of Baseline Gene Expression With Pathologic Respmentioning

confidence: 99%

CTLA-4 blockade and interferon-α induce proinflammatory transcriptional changes in the tumor immune landscape that correlate with pathologic response in melanoma

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Constitutive signaling from the EGFR promotes cell survival, proliferation [1], and invasiveness [2]. Aberrant EGFR signaling has been found in many human malignancies, including colorectal, lung, breast, and head and neck cancer [3,4].…”

Section: Introductionmentioning

confidence: 99%

Targeting Autophagy for Overcoming Resistance to Anti-EGFR Treatments

Kwon

Kim

Jung

et al. 2019

Cancers

View full text Add to dashboard Cite

Epidermal growth factor receptor (EGFR) plays critical roles in cell proliferation, tumorigenesis, and anti-cancer drug resistance. Overexpression and somatic mutations of EGFR result in enhanced cancer cell survival. Therefore, EGFR can be a target for the development of anti-cancer therapy. Patients with cancers, including non-small cell lung cancers (NSCLC), have been shown to response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and anti-EGFR antibodies. However, resistance to these anti-EGFR treatments has developed. Autophagy has emerged as a potential mechanism involved in the acquired resistance to anti-EGFR treatments. Anti-EGFR treatments can induce autophagy and result in resistance to anti-EGFR treatments. Autophagy is a programmed catabolic process stimulated by various stimuli. It promotes cellular survival under these stress conditions. Under normal conditions, EGFR-activated phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling inhibits autophagy while EGFR/rat sarcoma viral oncogene homolog (RAS)/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) signaling promotes autophagy. Thus, targeting autophagy may overcome resistance to anti-EGFR treatments. Inhibitors targeting autophagy and EGFR signaling have been under development. In this review, we discuss crosstalk between EGFR signaling and autophagy. We also assess whether autophagy inhibition, along with anti-EGFR treatments, might represent a promising approach to overcome resistance to anti-EGFR treatments in various cancers. In addition, we discuss new developments concerning anti-autophagy therapeutics for overcoming resistance to anti-EGFR treatments in various cancers.

show abstract

“…These results were in line with a previous report that demonstrated that AAMP promoted drug (icotinib and doxorubicin) resistance in NSCLC cells. 30 In addition, the metabolic states of cancer cells determine their fates in nutrient-poor environments. 41 AAMP KD further disrupted metabolic pathways involved in cancer progression (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…29 Another report suggested that AAMP interacted with EGFR and enhanced its phosphorylation, subsequently activating ERK1/2, which endowed non-small cell lung cancer (NSCLC) cells with enhanced proliferation ability and resistance to chemotherapies. 30 This research team also found that AAMP interacted with cell division cycle 42 (CDC42) and enhanced CDC42 activation by impairing the interaction of Rho GTPase-activating protein 1 (ARHGAP1) and CDC42, thereby promoting the migration and invasion of NSCLC cells. 31 However, the role of AAMP in CRC remains unexplored.…”

Section: Introductionmentioning

confidence: 95%

AAMP promotes colorectal cancer metastasis by suppressing SMURF2-mediated ubiquitination and degradation of RhoA

Liu

Lin

et al. 2021

Molecular Therapy - Oncolytics

View full text Add to dashboard Cite

Metastasis is considered the leading cause of cancer death due to the limited possibilities to therapeutically target this process. How the ubiquitination machinery contributes to metastasis remains underexplored. Angio-associated migratory cell protein (AAMP), a ubiquitously expressed protein involved in cell migration, has been reported to play oncogenic roles in breast and non-small cell lung cancer (NSCLC). However, the role of AAMP in colorectal cancer (CRC) has not been demonstrated. Here, we report that AAMP is aberrantly upregulated in metastatic CRC and that AAMP upregulation is correlated with the poor survival of CRC patients. AAMP knockdown significantly attenuated the migration and invasion of CRC cells, while AAMP overexpression led to the opposite effects. Mechanistically, we identified Ras homolog family member A (RhoA) as a target of AAMP. Smad ubiquitin regulatory factor (SMURF) 2 was previously found to be a CRC suppressor. Notably, we discovered here that SMURF2 acted as an E3 ubiquitin ligase to mediate the ubiquitination and degradation of RhoA. AAMP stabilized RhoA by binding to it and suppressing its SMURF2-mediated ubiquitination and degradation. Subsequently, the level of active RhoA was increased, thereby accelerating CRC cell migration and invasion. These findings indicate a new potential antitumor target for CRC.

show abstract

Angio-associated migratory cell protein interacts with epidermal growth factor receptor and enhances proliferation and drug resistance in human non-small cell lung cancer cells

Cited by 10 publications

References 29 publications

CTLA-4 blockade and interferon-α induce proinflammatory transcriptional changes in the tumor immune landscape that correlate with pathologic response in melanoma

CTLA-4 blockade and interferon-α induce proinflammatory transcriptional changes in the tumor immune landscape that correlate with pathologic response in melanoma

Targeting Autophagy for Overcoming Resistance to Anti-EGFR Treatments

AAMP promotes colorectal cancer metastasis by suppressing SMURF2-mediated ubiquitination and degradation of RhoA

Contact Info

Product

Resources

About