MYO1D binds with kinase domain of the EGFR family to anchor them to plasma membrane before their activation and contributes carcinogenesis
Authors: Nacksung Kim
Sung Jin Kim
Kyung Keun Kim
Kyung Hwa Lee
Hyuno Kang
Ik Joo Chung
Jeong A Bae
Hangun Kim
Eun Gene Sun
Young-Woo Seo
Yoo-Seung Ko
Keon Young Kim
Journal: Oncogene (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RTK; plasma membrane; MYO1D; EGFR; protein-protein interaction
Affiliations: Departments of Pharmacology, Chonnam National University Medical School, Gwangju, 61469, Korea., Departments of Hematology-Oncology, Chonnam National University Medical School, Gwangju, 61469, Korea., Departments of Pathology, Chonnam National University Medical School, Gwangju, 61469, Korea., Korea Basic Science Institute, Gwangju Center, Gwangju, 61186, Korea., College of Pharmacy, Sunchon National University, Sunchon, 57922, North Korea., Departments of Pharmacology, Chonnam National University Medical School, Gwangju, 61469, Korea. .

Abstract:  The cell surface receptor tyrosine kinase (RTK) exists in a dynamic state, however, it remains unknown how single membrane-spanning RTK proteins are retained in the plasma membrane before their activation. This study was undertaken to investigate how RTK proteins are anchored in the plasma membrane before they bind with their respective extracellular ligands for activation through protein-protein interaction, co-localization, and functional phenotype studies. Here we show that unconventional myosin-I MYO1D functions to hold members of the EGFR family (except ErbB3) at the plasma membrane. MYO1D binds only with unphosphorylated EGFRs and anchors them to underlying actin cytoskeleton at the plasma membrane. The C-terminal end region of the MYO1D tail domain containing a Œ≤-meander motif is critical for direct binding with kinase domain of the EGFR family, and expression of the tail domain alone suppresses the oncogenic action of full-length MYO1D. Overexpressed MYO1D increases colorectal and breast cancer cell motility and viability through upregulating EGFR level, and thereby promotes colorectal tumor progression in a syngeneic mouse model. MYO1D is upregulated in human colorectal cancer tissues from advanced stages. Collectively, molecular motor MYO1D plays a distinct role in the dynamic regulation of EGFR family levels by holding them at the plasma membrane before their activation. Overexpressed MYO1D contributes to colorectal carcinogenesis possibly as a novel oncogene and thus may serve as an additional target for suppression of RTK signaling in cancer treatment. 

Retracted: No

PubPeer comments:
 The authors presented some results in this paper based on a method reported in Ref[36]. However, this method is not reliable according to the comment on https: pubpeer.com publications CF7F949A30187DB3F0360CC1FD6ECF Hence, Theorem 4 cited in this paper should be carefully justified. Otherwise, the results based on Theorem 4 are not reliable.  , 
 For this problem, the link you provide has given clear explanation. In addition, this paper is focused on improving the consistency and consensus of reciprocal [0,1]-valued preference relations, and the main results of this paper are not based on Theorem 4. So it does not affect the main contribution of this paper. (MOD 2) is used to derive the priority vector of an incomplete reciprocal [0,1]-valued preference relation, and Theorem 4 gives the analytic solution of (MOD 2) through formula derivation. Actually, (MOD 2) can also be solved by using some software tools, which is often used. Even Theorem 4 can not obtain the priority vector in some special cases, (MOD 2) can also be solved by some software tools. So, it does not effect the main result of this paper. ,